Reichardt's research topic was the investigation of the orientation behaviour of insects. He saw it as a practical model system for the attempt to gain insight into the fundamental principles of information processing in biological organisms. Of course, Reichardt was not the first person to be interested in the behavioural control of insects and their dependence on vision and other sensory systems. But what set him apart from many others in his time and before him was his conviction that biological organisms should be understood primarily as information-processing systems. This was a view that grew out of the thinking of the information, communication and control sciences - "cybernetics" - that blossomed around the Second World War.

He saw the precise quantitative description of behaviour and its successful mathematical modelling as an indispensable prerequisite for trying to understand how a biological organism could perform the functions of interest. Based on well-founded models and the predictions they make, it would be possible to pursue the question of how sensory and nerve cells and their connections in networks make the model's performance possible at subordinate levels of analysis. It was this concept of the necessary interlocking of hierarchical levels of analysis that became the founding manifesto of the Max Planck Institute for Biological Cybernetics and was realised over many years in successful and internationally influential work at this institute and by partners at the university.

Reichardt's "level concept", which was later popularised by David Marr, stands in clear contrast to reductionist approaches in the neurosciences. They consider it sufficient to decipher elementary genetic, molecular and cellular principles, the combination of which, like a mosaic, would then make it possible to understand the biological basis of complex brain functions. This approach was bound to fail. Rather, fundamental understanding requires - as Reichardt demanded - an equal approach at different levels of analysis, from information processing using the toolbox of theory - now traded under the heading of "computational neuroscience" - to that of the genome.

Reichardt could hardly have imagined that his old institute, which nowadays seems almost tranquil and small, would one day become part of the exploding science and technology park of the "Obere Viehweide" - a location on a hill that is now amusingly known as "Cyber Valley". And the concept of intelligence, which is the centre of attention in Cyber Valley today, probably did not play a significant role in Reichardt's thinking either. But when we discuss today that intelligence as the result of information processing in machines is possibly indistinguishable from the result of information processing in the human brain - in other words, that there could be artificial intelligence that is indistinguishable from biological intelligence - then we are engaging in a discussion that was undoubtedly inherent in Reichardt's thinking.

Incidentally, the fact that Reichardt was able to exert this eminent influence on scientific developments is due to the fortunate coincidence that, against all probability, he survived the horrors of Nazi rule. Reichardt was drafted into a radio unit of the Wehrmacht immediately after graduating from high school in 1941 because of his knowledge of physics and technology. However, after he later made radio contact with the "enemy", he was arrested by the Gestapo in 1944. He was only able to avoid the threat of execution by luckily escaping and going into hiding in Berlin until the end of the war.

We at the Werner Reichardt Centre for Integrative Neuroscience at the University of Tübingen's Schnarrenberg have tried to commemorate the enduring importance of this Tübingen scientist for modern neuroscience by choosing his name for our centre. But should not we perhaps do more to keep alive the memory of someone whose internationally recognised life's work is closely associated with the scientific city of Tübingen? If you look at the streets in the area of Tübingen's science centres, you will notice that some of them bear the names of scientists who were undoubtedly important, but who have hardly any relevant biographical links to the city. Perhaps it would be time to reconsider some of the names and to name a street after a Tübingen scientist who stood out and was a pioneer in the development of a location-specific profile for neuroscience.

Peter Thier, Senior Professor of Cognitive Neurology at the Hertie Institute for Clinical Brain Research and founding spokesperson of the Werner Reichardt Centre for Integrative Neuroscience at the University of Tübingen

Poster presentations and talks are both welcomed, and the meeting will feature a keynote speaker from Tübingen.

Register here.

In der äußeren Erlebniswelt des Menschen tragen die Sinne gemeinsam zur Bildung von Erinnerungen bei. Der visuelle Reiz einer malerischen Landschaft, der Widerhall eines Lachens, die Wärme einer Umarmung – all diese Sinneseindrücke werden in einer Gehirnregion zusammengeführt, dem Hippocampus. Dieser Verarbeitungsprozess ist entscheidend, um flüchtige Sinneswahrnehmungen in dauerhafte Erinnerungen zu ver-wandeln. „Der Hippocampus arbeitet wie eine Art neuraler Kurator, der die Informationen integriert“, sagt Burgalossi. „Während des Erlebens wird im Hippocampus eine sogenannte Erinnerungsspur für eine Episode unseres Lebens angelegt.“

Frühere Annahmen in Frage gestellt

Um genauer zu verstehen, über welche Wege Sinnesinformationen in den Hippocampus gelangen, setzte das Forschungsteam an einer seiner Haupteingangsstrukturen im Gehirn an, dem vorderen Thalamus. „Wir wissen seit Jahrzehnten, dass dieser Bereich entscheidend ist für das episodische Gedächtnis. Patienten, die Schädigungen in dieser Hirnregion aufweisen, leiden unter Erinnerungsverlusten“, sagt Dr. Patricia Preston-Ferrer, eine der Studienautorinnen . Als Wissenschaftlerinnen und Wissenschaftler erstmals in den 1990er Jahren die Aktivitäten der Nervenzellen im vorderen Thalamus von Nagetieren aufzeichneten, entdeckten sie die dort angesiedelten Kopfrichtungszellen. „Bisher war man davon ausgegangen, dass diese ausschließlich das innere Abbild der Kopfbewegungsrichtung des Tieres in der Umgebung kodieren“, sagt Preston-Ferrer. „Doch nun zeigen unsere neuesten Experimente, dass diese Vorstellung nur ein unvollständiges Bild ergibt.“

Als das Tübinger Forschungsteam die elektrische Aktivität im Mäusegehirn aufzeichnete, stellte es fest, dass die Kopfrichtungszellen im Thalamus aktiv wurden, wenn sie die Maus Sinnesreizen aus-setzten. „Sowohl beim Vorspielen eines Tons als auch beim Berühren eines Tasthaares an der Schnauze der Maus wurden gezielt und zuverlässig und mit bemerkenswert kurzer Verzögerung nur die Kopfrichtungszellen aktiviert“, sagt der CIN-Forscher und Mitautor der Studie Giuseppe Balsamo. „Wir waren überrascht, da man jahrzehntelang annahm, dass die Hirnregion im vorderen Thalamus auf Sinnesreize kaum reagiert.“

Szenario verbindet inneren Kompass und episodisches Gedächtnis

Außerdem ergaben die Experimente, dass im vorderen Thalamus nur die Kopfrichtungszellen auf Sinnesreize antworteten, andere Nervenzellen jedoch nicht. „Daher wissen wir, dass die Kopfrich-tungszellen eine besondere Funktion haben müssen“, sagt der CIN-Forscher und Mitautor der Stu-die Dr. Eduardo Blanco-Hernandez. „Ihre Aufgabe muss über die Funktion als innerer Kompass hin-ausgehen.“ Auf eine zunehmende Erregung der Maus oder auf soziale Kontakte wie dem Zusam-mentreffen mit einem Artgenossen reagierten die Kopfrichtungszellen mit gesteigerter Aktivität. „Es ist bekannt, dass große Aufmerksamkeit und Gefühle einen großen Einfluss auf die Entstehung von Erinnerungen und deren Qualität haben. In solchen Situationen erinnern wir uns viel lebhafter als in einem unbeteiligten, passiven Zustand“, sagt Blanco-Hernandez.

Insgesamt weisen die neuen Ergebnisse darauf hin, dass die Kopfrichtungszellen im Thalamus einen entscheidenden Beitrag zur Aufnahme und Weiterleitungvon Sinnesinformationen, Aufmerksamkeits- und Erregungszuständen in das System des episodischen Gedächtnisses bilden könnten. „Um zu verstehen, wie eine Erinnerungsspur gelegt wird, müssen wir die Wege und beteiligten Nervenzellen kennen, die Basisinformationen in den Hippocampus weitergeben“, sagt Burgalossi. „Wir gehen nun davon aus, dass der innere Kompass einen Hauptknoten in diesem Prozess darstellt.“ Ob dieser Knoten beeinflusst werden könnte, etwa auch zu therapeutischen Zwecken, um Erinnerungen besser bilden und abrufen zu können, müsse weiter untersucht werden.

Publikation:

Eduardo Blanco-Hernández, Giuseppe Balsamo, Patricia Preston-Ferrer and Andrea Burgalossi: Sensory and behavioral modulation of thalamic head-direction cells. Nature Neuroscience, https://doi.org/10.1038/s41593-023-01506-1

Kontakt

Prof. Dr. Andrea Burgalossi
Universität Tübingen
Institut für Neurobiologie
Werner Reichardt Centrum für Integrative Neurowissenschaften (CIN)
 Telefon +49 7071 29-88797
 andrea.burgalossi@cin.uni-tuebingen.de

Lecturer: Yulia Oganian (Audition) and Cornelius Schwarz (Touch)

Cognitive Neuroscience of Human Verbal Communication (Oganian)
Systems Neurophysiology (Schwarz)
Werner Reichardt Centre for Integrative Neuroscience

Location: HIH Seminar Room E2 (2.310)
Wed., 17.05.2023, 2pm

You can find out more about the 11th CIN-NIPS Symposium here.

Institute for Physiology I, Universität Freiburg
https://www.veitlab.de/

Location: HIH-Seminarraum E5
Mittwoch, 25.01.2023, 14:00 Uhr

Host: Lena Veit (lena.veitspam prevention@uni-tuebingen.de) Bitte schreiben Sie Frau Veit an, wenn Sie mit der Referentin Kontakt halten möchten)

Decision and Awareness Group,
Cognitive Neuroscience Laboratory,
German Primate Center (DPZ)
http://www.dpz.eu/dag

Location: HIH-Seminarraum E2 (2.310)
Mittwoch, 23.11.2022, 2pm

Host: Ziad Hafed (ziad.hafedspam prevention@cin.uni-tuebingen.de) Bitte schreiben Sie Herrn Hafed an, wenn Sie mit dem Referenten Kontakt halten möchten)

Internal state changes pupil size

The eyes are also often referred to as the “windows to the soul”. In fact, there is a grain of neurobiological truth to this. Pupil size is not only influenced by sensory stimuli such as sunlight, but also by our current internal state such as fear, excitement or attention. Interestingly, these state-dependent changes in pupil size are observed not only in humans but in many other vertebrates.

Artificial intelligence for data analysis

In experiments, an international team of researchers from the universities of Tübingen and Göttingen in Germany together with scientists from Baylor College of Medicine, investigated how state-dependent changes in pupil size affect the vision of mice. While the eyes convert light to neural activity, it is the brain which is crucial for the interpretation of visual scenes. In their experiments, the researchers showed mice different colored images and recorded the activity of thousands of individual neurons within the visual cortex, a particularly relevant brain area for visual perception. Based on these recordings, they used deep neural networks to create a computer model as a digital twin of the cortex, simulating the responses of large numbers of neurons in the brain. They then used this computer model to identify the optimal visual light stimulus for each neuron - each neuron's "favorite image".

Effects on visual perception

This model revealed something quite interesting: When the mice dilated their pupils due to an alert state of mind, the color sensitivity of the neurons to change from green to blue light within seconds. This was particularly true for neurons that sample stimuli from the upper hemisphere used to observe the sky. In subsequent experiments they were able to verify that this also happens in the real biological neurons.

With the help of eye drops that dilate the pupil, the researchers were then able to simulate the higher sensitivity to blue light even for a quiet brain state. “These results clearly demonstrate that pupil dilation due to an alert brain state can directly affect visual sensitivity and probably visual perception as well. The mechanism here is that a larger pupil lets more light into the eye, recruiting different types of photoreceptors in our retina and thus indirectly changing the color sensitivity in the visual cortex," explains Dr. Katrin Franke, research group leader at the Institute for Ophthalmology Research at the University of Tübingen and first author of the study.

But what are the benefits of this change in visual sensitivity? Konstantin Willeke, shared first author of the study and member of the research group led by Dr. Fabian Sinz explains: "We were able to show that the higher neuronal sensitivity to blue light probably helps the mice to better recognize predators against a blue sky.”  The computer model that the researchers created can also prove useful in many ways: "We assume that our model can be used for further experiments to understand visual processing."

"Combining high throughput experimental data with AI modeling is opening a new era in neuroscience research. They enable us to extract accurate digital twins of real-world biological systems from data." Willeke adds. “With these digital twins, we can perform an essentially unlimited number of experiments in the computer. In particular, we can use them to generate very specific hypotheses about the biological system which we can then verify in physiological experiments.”

The finding that brain state-related changes in pupil size affect visual sensitivity has implications for our understanding of vision well beyond predator detection in mice. Further research questions now arise as to how perception in numerous other animals is influenced by this effect. The pupils in our eyes could thus not only be a window into the soul, but also change the way we perceive the world from moment to moment depending on our inner state of mind.

Referent: Mario Prsa

Sensorimotor Neuroscience Laboratory
Université de Fribourg, Switzerland
https://www.unifr.ch/med/de/research/groups/prsa/

Location: HIH Seminar Room E2 (2.310)
Mittwoch, 21.09.2022, 2pm

Host: Cornelius Schwarz (cornelius.schwarzspam prevention@uni-tuebingen.de) Bitte schreiben Sie Herrn Schwarz an, wenn Sie mit dem Referenten Kontakt halten möchten)

„Wir Menschen verlassen uns in hohem Maße auf das foveale Sehen“, erklärt Erstautor Konstantin Willeke. „Das ist der Bereich, auf den wir unseren Blick richten. Hier sehen wir Objekte am schärfsten. Menschen und Gegenstände, die außerhalb unserer Blickrichtung liegen, nehmen wir mit zunehmendem Abstand verschwommener wahr.“ Zur Veranschaulichung empfiehlt Willeke folgenden Selbsttest: Wenn wir jemandem direkt in die Augen schauen und ihn bitten, farbige Stifte neben sein Ohr zu halten, erkennen wir nicht, wie viele Stifte er hochhält oder welche Farben sie haben. Die Augenfarbe unseres Gegenübers könnten wir stattdessen problemlos beschreiben.

Doch scheinen nicht alle Sehinformationen aus der zentralen Blickrichtung anschließend gut im Gedächtnis zu bleiben. Das stellten die Tübinger Hirnforschenden fest, als sie untersuchten, mit welcher Genauigkeit foveale Bilder im Kurzzeitgedächtnis repräsentiert werden.

Sie präsentierten gesunden Versuchspersonen einen kleinen Lichtreiz auf einem Bildschirm. Dieser konnte an ganz unterschiedlichen Stellen erscheinen. Nachdem er verschwunden war, sollten die Personen aus dem Gedächtnis die Position angeben.

Das Ergebnis: Die größten Abweichungsfehler machten die Versuchspersonen bei den Lichtreizen, die im Bereich des fovealen Sehens präsentiert wurden. „Das lässt vermuten, dass die Repräsentation im Kurzzeitgedächtnis stark verzerrt ist,“ so Studienleiter Hafed. „Die Verzerrungen spiegeln wahrscheinlich den Aufbau unseres Sehsystems wider.“

Um eine hohe visuelle Auflösung zu erreichen, würden Sehreize aus der Sehgrube von einer verhältnismäßig großen Anzahl an Nervenzellen im Gehirn verarbeitet. Ihre mentale Repräsentation sei daher vergrößert. Reize aus den Randbereichen des Gesichtsfeldes würden hingegen von weniger Nervenzellen verarbeitet, ihre mentale Repräsentation sei folglich kleiner. „Orientiert sich die Versuchsperson bei der Gedächtnisaufgabe im mentalen Raum und überträgt die Entfernungen dann auf die Außenwelt, kommt es zu den relativen Abweichungsfehlern“, erklärt Hafed. „Diese sind für foveale Sehreize logischerweise größer als für Sehreize aus der Peripherie.“

Die neuen Erkenntnisse sind hilfreich, um neurologische Erkrankungen besser zu verstehen, bei denen etwa die Körperwahrnehmung gestört ist. Sie sind ebenfalls für den IT-Bereich interessant. So könnten sie helfen, virtuelle Realitäten zu optimieren. Die präsentierten Bilder könnten mithilfe eines Eyetrackers – eines Geräts, das Blickbewegungen aufzeichnet und analysiert – etwa so aufgebaut werden, dass bestimmte Bereiche besser oder schlechter erinnert würden.

„Als Menschen empfinden wir das Sehen als mühelos,“ sagt Hafed. „Das ist aber eine Illusion. Hinter unserem subjektiven Gefühl verbirgt sich eine enorm komplexe rechnerische Verarbeitung im Gehirn.“ Neben Hafed und Willeke waren Dr. Araceli Cardenas und Dr. Joachim Bellet an der Studie beteiligt.

Originalpublikation
Willeke, K.F et al. (2022): Severe distortions in the representation of foveal visual image locations in short-term memory. PNAS 119 (24) e2121860119 doi: https://www.pnas.org/doi/10.1073/pnas.2121860119

Kontakt:
Prof. Dr. Ziad M. Hafed
Universität Tübingen
Hertie-Institut für klinische Hirnforschung
CIN
Telefon +49 7071 29-88819
ziad.m.hafedspam prevention@cin.uni-tuebingen.de

Organisation:

• Werner Reichardt Centrum für Integrative Neurowissenschaften an der Universität Tübingen
• Hertie-Institut für klinische Hirnforschung
• Eberhard Karls Universität Tübingen

Am Donnerstag, 7. Juli um 19:15 Uhr im Audimax (Neue Aula, Geschwister Scholl Platz). Die interessierte Öffentlichkeit ist herzlich eingeladen. Es ist keine Anmeldung nötig, es gilt Maskenpflicht.

Das Konzept der „Liebe“ und romantische Beziehungen sind nicht nur Gegenstand psychologischer und soziologischer, sondern auch neurowissenschaftlicher Forschung. Die Neurowissenschaften erforschen neurobiologische und genetische Grundlagen der Liebe und der Mechanismen, auf denen unser Sozialverhalten beruht. Neurowissenschaftlerinnen und Neurowissenschaftler behaupten sogar, die neurologische Fundierung der Liebe sei eines der Phänomene, die am besten verstanden sind. Aus beiden Perspektiven, der Soziologie und der Neurowissenschaft, können wir also aktuelle Antworten auf die Frage erwarten, wie eine angemessen komplexe Beschreibung des Konzepts „Liebe“ aussehen kann.

Wie also hat sich das Konzept der Liebe verändert – insbesondere durch Dating-Plattformen als zentralem Ort für die Anbahnung romantischer Kontakte? Gibt es einen kulturellen Einfluss auf die Liebe selbst, oder nur auf die Art und Weise, wie wir sie suchen und zeigen? Und können NeurowissenschaftlerInnen und SoziologInnen voneinander lernen, wonach sie suchen sollten, wenn sie erforschen, was Liebe heute bedeutet? Dies sind einige der Fragen, die Eva Illouz und Larry Young diskutieren werden. Das Gespräch moderiert Wissenschaftsjournalistin Alison Abbott (Nature).

Im Vorfeld des CIN Dialogs findet um 16 Uhr die feierliche Eröffnung des Cognitive Science Centers (CSC) Tübingen mit dem Vortrag „Natural concepts in humans and in machines: A design perspective“ des renommierten Kognitionswissenschaftlers Professor Peter Gärdenfors (Lund Universität) statt.

Eva Illouz ist Professorin für Soziologie an der Hebräischen Universität Jerusalem und Directrice d'études an der École des hautes études en sciences sociales (EHESS) in Paris. Ihre Forschungsschwerpunkte sind die Soziologie der Kultur, der Geschlechter, des Kapitalismus sowie die Geschichte und Soziologie der Emotionen. In ihrer Arbeit untersucht sie u.a., wie die öffentliche Kultur und der Kapitalismus das Gefühlsleben prägen, die Kommerzialisierung der Romantik sowie die Bedeutung von Freiheit, Wahlmöglichkeiten und Individualismus in der modernen Welt. Die Zeit wählte sie zu einer der 12 Intellektuellen, die das Denken der Zukunft prägen werden.

Larry Young ist Direktor des Center for Translational Social Neuroscience (CTSN) und des Silvio O. Conte Center for Oxytocin and Social Cognition an der Emory University. Youngs Forschung befasst sich mit den genetischen, zellulären und neurobiologischen Mechanismen, welche Beziehungen zugrunde liegen und das Sozialverhalten regulieren. Er hat die zentrale Rolle der Neuropeptide Oxytocin und Vasopressin bei der neuronalen Verarbeitung sozialer Signale identifiziert und erforscht Verbindungen zur Grundlage von Sucht. Dieses Verständnis nutzt sein Labor um Medikamente zur Behandlung psychiatrischer Störungen zu finden.

Alison Abbott promovierte in Pharmakologie an der Universität von Leeds. Sie war Redakteurin von Trends in Pharmacological Sciences, und von 2014 bis 2018 Vorsitzende des FENS-Kommunikationsausschusses. Für ihre Arbeit hat sie zahlreiche Auszeichnungen erhalten, darunter den Euroscience Science Writers Award (2009), den Medical Journalists Association Award (2015) und den ABSW Science Journalist of the Year Award (2018).

Über die CIN Dialogues

Immer häufiger wird menschliches Verhalten und Handeln erfolgreich auf neuronale Prozesse zurückgeführt. Das stellt die Geistes- und Sozialwissenschaften, in deren Kompetenzbereich solche Fragen bislang fielen, vor Herausforderungen, bietet aber auch die einmalige Chance zu interdisziplinärer Forschungsarbeit. Die CIN Dialogues tragen dazu bei, den Austausch zwischen Neurowissenschaften und Geistes- und Sozialwissenschaften über den rein akademischen Bereich hinaus sichtbar zu machen und in die Gesellschaft zu tragen. (www.cin.uni-tuebingen.de / https://uni-tuebingen.de/de/218658)

Kontakt:

Prof. Dr. Andreas Bartels
Universität Tübingen
Werner Reichardt Centre for Integrative Neuroscience
Vision and Cognition
Telefon +49 (0)7071 29- 89168
andreas.bartelsspam prevention@cin.uni-tuebingen.de

Dr. Niels Weidtmann
Universität Tübingen
College of Fellows, Director
Telefon +49 (0)7071 29-77239
niels.weidtmannspam prevention@cof.uni-tuebingen.de
www.uni-tuebingen.de/college-of-fellows

Die Daten auf einen Blick

CIN DIALOGUES AT THE INTERFACE OF THE NEUROSCIENCES AND THE ARTS AND HUMANITIES – ein interdisziplinäres Gespräch –

Gäste:
Professor Dr Eva Illouz, Hebrew University of Jerusalem
Professor Dr Larry Young, Emory University, Atlanta
Moderation: Dr Alison Abbott, Nature

7. JULI 2022, 19.15 Uhr
Audimax, Neue Aula
Geschwister-Scholl-Platz, Tübingen

Organisation:

• Werner Reichardt Centrum für Integrative Neurowissenschaften an der Universität Tübingen
• College of Fellows der Universität Tübingen

“The existence of head-direction cells was documented more than 30 years ago in rodents. Much like a compass, these neurons follow the movement of the animal in its environment, thus giving rise to an internal representation of direction in the brain,” Dr. Patricia Preston-Ferrer explains. “If you are to understand how neurons work in the brain, you first need to make them visible,” she adds. In order to understand information processing in the brain – the software – you need to resolve the underlying brain circuits – the hardware. As early as 2016, the team established an experimental approach for making head-direction neurons visible under the microscope.

Corresponding structures in the human brain

Head-direction neurons are known to be preferentially located in the presubiculum, a specialized area of the cortex. “We were very surprised by finding that the mouse presubiculum was not homogeneous, but clearly divided into modules”, says CIN researcher Giuseppe Balsamo. “We identified two different types of modules which were molecularly distinct, and were differently interconnected with other parts of the brain.” The team found that these modules were present not only in the rodent brain, but also in the human brain.

By labelling individual head-direction neurons, the authors made two striking observations. Firstly, head-direction neurons were found only in one cortical module, pointing to a precise structure-function organization of the presubicular cortex. Second, this module type was densely innervated by one particular nucleus of the thalamus, which is involved in the processing of visual landmark information. “We know that efficient navigation relies on the use of an internal compass, plus external visual landmark information” says Professor Andrea Burgalossi, head of a CIN research unit. “We may have found the place in the brain where the internal sense of direction and visual information are combined to support navigation.”

Switching off the compass

The team also found that, whenever they artificially perturbed the activity of the cortical modules, head-direction neurons became suddenly silent. “It seemed that our manipulation had switched off the internal compass” says Dr. Eduardo Blanco-Hernandez. Yet not all head-direction neurons were silenced. “We currently do not know whether silenced and stable head-direction neurons serve different functions during behavior, but clearly the internal compass has a more complex structure than previously assumed.”

“We have gained insights into fundamental organization principles of the cortex,” says Dr. Preston-Ferrer. In fact, modularity has been observed in other cortical areas. The cortex is a thin layer of neural tissue on the surface of the brain, which is primarily responsible for high-order cognitive functions. By focusing on the head-direction system, the team was able to map one of these functions – internal representation of direction – onto the underlying cortical structure. “Now it will be important to understand when and how the presubicular cortical modules emerge during development”, says Prof. Burgalossi “and whether they are disrupted in neurodegenerative disorders, like Alzheimer’s disease, where problems with the internal sense of direction are one of the earliest signs.”

Publication: Giuseppe Balsamo, Eduardo Blanco-Hernández, Feng Liang, Robert Konrad Naumann, Stefano Coletta, Andrea Burgalossi and Patricia Preston-Ferrer: Modular microcircuit organization of the presubicular head-direction map. Cell Reports 39, 110684 April 12. doi.org/10.1016/j.celrep.2022.110684

Organization:

• University of Tübingen
• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neural Circuits and Behavior

Contact: Dr. Andrea Burgalossi

Herzlichen Glückwunsch!

Die Pressemitteilung kann hier gelesen werden.

Dr. Vlasits erforschte als Postdoc von 2018-2021 amakrine Zellen im Labor von Thomas Euler. Derzeit ist sie Postdoktorandin an der Northwestern University, Illinois.

Matthias Bethge, spokesperson for the research center, is very pleased that the research program will continue to receive funding. “We are making great progress in understanding biological vision and in the field of robust machine vision. This also opens the door to the development of more reliable AI applications,” he said.

In the second funding period starting 2021, the German Research Foundation will fund 12 scientific projects, one infrastructure project and one transfer project with Zeiss Vision with total funding of over €9 million.

The CRC also includes several groups from the Institute for Ophthalmic Research (Prof. Philipp Berens, Prof. Thomas Euler, Dr. Katrin Franke, Prof. Frank Schaeffel, Prof. Katarina Stingl, Dr. Christina Schwarz and Prof. Sigfried Wahl).

Background

Human visual perception is amazingly robust: Even in highly variable environments, we are able to make reliable inferences about the spatial arrangement of the world from limited visual information. To achieve this, our brain must perform complex computations. Artificial vision systems, in turn – as used, for example, in self-driving cars – are making steep progress in reproducing the visual skills of humans. The goal of this centre will be to better understand the principles and algorithms that enable robust visual inference both in humans and machines.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Contact: Prof. Dr. Matthias Bethge

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Animal Physiology

Contact: Prof. Dr. Andreas Nieder

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

Press release can be found here

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Computational Sensomotorics (Alumni)

Contact: Prof. Dr. Martin A. Giese

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Physiology of Active Vision (Alumni)

Contact: Prof. Dr. Ziad Hafed

It is one of those things that children ask their parents and that have parents scratching their heads: Mommy, why can’t I tickle myself? Even the most ticklish among us will have noticed that this is not possible. The reason for this has been known for a long time: touch receptors in the touched part of skin may feel the touch just as any other, but somewhere along the way to higher brain areas where this touch is ‘perceived’, the feeling is altered. This is because when our finger touches our own skin, our brain anticipates the touch and reduces the signal. This phenomenon is called sensory gating.

Sensory gating has attracted much interest in different branches of neuroscience and psychology. There is evidence that schizophrenic disorders impair sensory gating, leading to hallucinations where one’s own voice seems to be that of somebody else. The phenomenon addresses the philosophical question about how we construct our world at the most basic level: do we faithfully represent stimuli from the outside world, or do we have preconceptions about the world that we use like a template, only noticing when they fail to account for what we see or feel? Psychology has found evidence to support both lines of arguing.

“The reason these questions are so hard to answer is because the predictions that the brain generates are very difficult to pinpoint”, says Cornelius Schwarz, head of the “Systems Neurophysiology” group at the University of Tübingen’s Werner Reichardt Centre for Integrative Neuroscience (CIN) / Hertie Institute for Clinical Brain Research (HIH). ‘We know that in active perception, somewhere along the line, signals are gated. But where that gating originates, at what point the signals coming from the sensory organs are intercepted and what neuronal pathways these signals take, are questions we have spent years trying to answer.’

To address these questions Schwarz and Shubhodeep Chakrabarti, who was awarded a DFG independent investigator grant to lead the project, investigated the rat’s whisker system. With their whiskers, rats actively feel their surroundings, detecting obstacles and navigating even in completely dark environments. Chakrabarti and Schwarz now let their rats detect an object using just a single whisker. Then, in some trials the object was moved to touch the whisker (passive perception), while in others the rat would only detect the object by moving its whisker (active perception). During each trial, they recorded the activity of individual cells in the rat’s brainstem using hair-thin implanted electrodes. Whenever the rat actively touched the object, recorded signals were much weaker than in those cases where the object was touched passively: sensory gating was thus clearly shown to be at work in the brainstem.

“It is extremely interesting that sensory gating actually happens in the brainstem, and not further along the neuronal pathway into the brain”, says Chakrabarti. “We would not necessarily have expected the sensory signal to be intercepted and modulated this early.” Furthermore, the scientists were able to show where the gating originates: in the so-called primary somatosensory cortex. This higher brain area is situated on top of the brain and is present in both rats and humans. It is responsible for our perception of pressure, temperature, and some aspects of pain. In rats whose somatosensory cortex was damaged, sensory signals recorded in the brainstem were not gated.

Chakrabarti explains what this means: “The somatosensory cortex, where feeling takes place, modifies its own input by sending out a gating signal which predicts expected touch, ahead of time, all the way out to the brainstem. Then, when the actual signal from the whisker arrives to tell the somatosensory cortex ‘attention, we just detected an object!’, it has to pass through the brainstem. There, a temporary gate or checkpoint puts a label on the signal: ‘this detection was expected to a degree, it is of limited importance.’ Clearly, sensory perception is not a one-way street.”

Chakrabarti and Schwarz are now already engaged in a host of follow up questions. They want to study the effects of attention and motivation next: does the somatosensory cortex also gate signals if there is a reward at stake? Could it be that, if the subject focuses intensely on relevant signals, gating will result in signal enhancement rather than reduction? If so, it could mean that cognitive functions such as desires and expectations have a very large influence on our perception of the world.

Publication:
Shubhodeep Chakrabarti, Cornelius Schwarz: Cortical Modulation of Sensory Flow During Active Touch in the Rat Whisker System. Nature Communications 9: 3907. doi: 10.1038/s41467-018-06200-6

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Systems Neurophysiology

Contact: Prof. Dr. Cornelius Schwarz

Mit einem ganz anderen Aspekt der Hirnforschung befasste sich Ann-Christin Wendeln vom Hertie-Institut für klinische Hirnforschung in ihrer ausgezeichneten Studie. Sie untersuchte die Reaktionen der Immunzellen im Gehirn auf Entzündungsreize, die im Körper und nicht im Gehirn selbst verabreicht wurden. Die Studie ergab, dass solche Reize verschiedene Prozesse in den Immunzellen des Gehirns, den Mikroglia, einleiten, die zu einer langfristigen Reprogrammierung der Mikroglia führen. Bei genveränderten Mäusen, die als Modell der Alzheimer-Erkrankung dienen, verschlimmerten bestimmte Entzündungsreize die für die Krankheit typische Plaque-Bildung im Gehirn. In ähnlicher Weise veränderte eine solche Immunstimulation die Krankheitscharakteristika nach einem Schlaganfall. Die Forscherin konnte gemeinsam mit ihren Kollegen den Nachweis erbringen, dass die Mikroglia im Gehirn der Sitz des angeborenen Immungedächtnisses sind. Außerdem ergab ihre Studie, dass auf den Körper einwirkende Entzündungsreize Langzeitveränderungen im Immungedächtnis des Gehirns auslösen und darüber Einfluss nehmen auf den Verlauf neurologischer Erkrankungen. Die Ergebnisse liefern wichtige Hinweise für die Erforschung von neurologischen Erkrankungen, die mit einer entzündlichen Komponente zusammenhängen.

Mit der Verleihung der Attempto-Preise beginnt am Mittwoch, 17. Oktober 2018, um 15 Uhr im Großen Senat der Neuen Aula (Geschwister-Scholl-Platz, 72074 Tübingen) die diesjährige Mitgliederversammlung des Universitätsbundes. Medienvertreterinnen und Medienvertreter sind herzlich eingeladen.

Der Attempto-Preis wurde 1983 von dem Psychiater Konrad Ernst und seiner Ehefrau Dorothea gestiftet. Er wird jährlich an Nachwuchswissenschaftlerinnen und -wissenschaftler für herausragen-de Arbeiten über Hirnleistungen und deren Störungen vergeben, die an der Universität Tübingen und an den der Universität verbundenen Tübinger Einrichtungen der Max-Planck-Gesellschaft entstanden sind. Zurzeit werden jährlich zwei Nachwuchswissenschaftlerinnen oder -wissenschaftler mit einem Preisgeld in Höhe von je 10.000 Euro ausgezeichnet. Das Geld kann zur Förderung ihrer weiteren wissenschaftlichen Karriere eingesetzt werden.

Publikationen:

Fedorov L, de la Rosa S, Chan DS, Giese M, Bülthoff H: Adaptation aftereffects reveal representations for contingent social actions. PNAS 2018, 115(29):7515-7520; doi: 10.1073/pnas.1801364115.

Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, Wagner J, Häsler LM, Wild K, Skodras A, Blank T, Staszewski O, Datta M, Pena Centeno T, Capece V, Islam MR, Kerimoglu C, Staufenbiel M, Schultze JL, Beyer M, Prinz M, Jucker M, Fischer A, Neher JJ: Innate immune memory in the brain shapes neurological disease hallmarks. Nature 2018, 556:332-338

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research
• University of Tübingen
• Max Planck Institute for Biological Cybernetics

Reseach Group: Computational Sensomotorics

„Um eine Bewegung optimal durchzuführen, kombiniert das Kleinhirn Informationen unterschiedlicher Art“, erklärt Studienleiter Thier. Sie laufen in den sogenannten Purkinjezellen zusammen. Infolgedessen senden die Zellen selbst zwei verschiedene Signale aus. Das erste ist ein hochfrequentes Signal, das Informationen über die Position, Geschwindigkeit und Beschleunigung einer Bewegung weiterleitet. Das zweite ist ein niederfrequentes Signal, das entsteht, wenn die Zellen Informationen aus den sogenannten Kletterfasern erhalten. „Bei dem Kletterfasersignal war bisher unklar, ob es sich um ein Fehlersignal handelt, das Abweichungen in dem durchgeführten Bewegungsablauf signalisiert – oder ob es ein ‚Gedächtnissignal‘ ist, das zeigt, wieviel in einer neuen Situation bereits gelernt wurde“, so Thier.

Um die Aufgabe des Kletterfasersignals zu entschlüsseln, maßen die Forscher die Aktivität einzelner Purkinjezellen im Gehirn von Rhesusaffen. Diese verfolgten dabei einen Punkt auf einem Bildschirm, der mit einem bestimmten Abstand von der Mitte nach oben, unten, links oder rechts sprang. Der Punkt war so programmiert, dass der Abstand sich hin und wieder zufällig veränderte. In diesen Durchgängen blieb das Blickziel nicht dort, wo der Affe es erwartete, sondern es verlagerte sich etwas nach außen oder nach innen. Als Folge landeten seine Augen nicht mehr auf dem Ziel, sondern leicht daneben: Ein Bewegungsfehler war ausgelöst. Mit diesem Versuchsaufbau konnten die Wissenschaftler klären, unter welchen Bedingungen und in welcher Form das Kletterfasersignal entsteht.

„Wir sahen, dass das Kletterfasersignal zum einen in dem Moment gesendet wird, in dem ein Bewegungsfehler stattfindet. Es ist also ganz klar ein Fehlersignal“, erklärt Erstautor Junker. Die Wissenschaftler be-obachteten das Signal aber noch zu einem anderen Zeitpunkt. Kurz bevor eine Augenbewegung erneut ausgeführt wird, wird es ebenfalls gesendet – und zwar abhängig von dem Fehler, der in der vorherigen, identischen Bewegung gemacht wurde. „Gemäß dem Spruch ‚Vorsicht, das lief letztes Mal schief‘ erinnert sich das Kleinhirn auf diese Weise an vergangene Fehler“, erläutert Junker. Dadurch könne die aktuelle Bewegung direkt angepasst und verbessert werden.

Das Kletterfasersignal erfüllt also beide zugeschriebenen Rollen und ist Fehler- und Gedächtnissignal zugleich. „Jede Art von Bewegung erfordert ein Höchstmaß an Präzision und Verlässlichkeit. Diese kann nur aufrechterhalten werden, wenn stets auch die kleinsten Unzulänglichkeiten erfasst und genutzt werden, um zukünftige Fehler zu vermeiden“, so Thier.

Patienten, deren Kleinhirn aufgrund Multipler Sklerose, Schlaganfällen oder Hirntumoren geschädigt ist, besitzen diese Fähigkeit nicht oder nur eingeschränkt. „Eine Ataxie ist die Folge: Die Betroffenen können sich zwar noch bewegen, sind jedoch unsicher und wenig präzise. Das hat erhebliche Auswirkungen auf ihren Alltag“, berichtet Thier. Neben Augenbewegungen gehört auch das Heben einer Tasse, Zähneputzen, Tastaturschreiben oder Sprechen zu den Bewegungen, die vom Kleinhirn kontrolliert werden. Derzeit können Ataxien nicht behandelt werden. Nur ein besseres Verständnis der Art und Weise, wie das Kleinhirn Bewegungen optimiert, ermöglicht langfristig die Entwicklung effektiver Rehabilitationsmaßnahmen. Für die Wissenschaftler keine leichte Aufgabe: „Das Kleinhirn ist sehr komplex und alles andere als klein – es enthält wesentlich mehr Nervenzellen als der gesamte Rest unseres Gehirns“, sagt Thier.

Organization:

• Hertie Institute for Clinical Brain Research
• Werner Reichardt Centre for Integrative Neuroscience

Contact: Prof. Dr. Hans-Peter Thier

“The way that the superior colliculus processes visual input from our surroundings is specifically tuned to what we need to efficiently orient ourselves”, Prof Ziad M. Hafed introduces his object of study. The leader of a research team at the CIN and HIH has been investigating the primate visual system for years. In primates – and thus in us humans –, conscious seeing is primarily jumpstarted in the visual cortex, a well-known area of the cerebral cortex. But based on their own earlier studies, Hafed’s research group was convinced that the “small upper hill” in the brainstem maintains very important visual functions as well. For instance, it plays a paramount role in the visual system of fish and amphibians. In mammals and especially in primates, however, this brain area has been thought to mostly just control eye movements and attention.

But Hafed and his team are convinced that the superior colliculus plays a central role in visually-driven environmental orientation and navigation as a whole. “If a brain area controls eye movements, then it seems intuitive that it also fulfills important functions in general orienting behaviour”, Hafed puts it, adding: “But to do so, it must also be able to process visual information.”

To investigate this hypothesis, the Hafed lab performed neurophysiological experiments with rhesus macaques, whose visual system is very similar to our own. The researchers investigated how individual brain cells (neurons) responded to different visual stimuli. Would changes in features such as the image’s orientation, its contrast and background, and other image properties make a difference in how superior colliculus neurons responded? If this area is responsible for spatial orientation, neurons here must respond especially quickly to those stimuli towards which we would need to direct our attention first. In natural environments, our attention is primarily focused on the most general features first: is there an open space in front of us, are there obstacles, is there a figure or a face? In order for us to cope with our surroundings, our brain must process such features as quickly as possible; fine details can wait for closer inspection.

For this reason, the researchers observed how the neurons they were investigating responded to coarse image features with low amounts of variation in visual information – or (as the scientists call it) with low spatial frequency. This might be the case with large swathes of forest or sky or clouds in our surroundings. The result: neurons in the superior colliculus do in fact respond to visual stimuli with low spatial frequency the quickest. Naturally, the observed set of neurons did not all respond identically, some going so far as to show a stronger overall response to high spatial frequency stimuli. But even these high-frequency specialists still responded more quickly to the presentation of coarse image patches: the “turbo boosting” of neural responses to low-frequency stimuli took priority over actually sensing the image content itself. This is important, as the turbo-boosted signal was also instrumental in determining how efficiently eye movements are made.

Thus, the “little hill” in our brain has the ability to analyse visual patterns – a capability most scientists would have denied this brain area could have. “We have added evidence that the primate superior colliculus is not merely an organ of motor control,” says Hafed, “but a visual structure that may be just as important as the primary visual cortex in allowing us to function in our everyday surroundings.”

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Physiology of Active Vision

Contact: Prof. Dr. Ziad Hafed

Um herauszufinden, welche neuronalen Mechanismen bei der Gestaltwahrnehmung eine Rolle spielen, haben die ForscherInnen den TeilnehmerInnen ihrer Studie zweideutige visuelle Stimuli gezeigt und dabei mit Hilfe der funktionellen Magnetresonanztomografie (fMRT) die Gehirnaktivität der ProbandInnen beobachtet. Als Stimuli wurden insgesamt drei unterschiedliche bewegte grafische Darstellungen verwendet, die jeweils zwei- und dreidimensional gesehen bzw. interpretiert werden können.

„Bei allen drei Stimuli fanden wir eine gemeinsame Aktivität im IPS, wobei sie bei der komplexen, dreidimensionalen Interpretation in jedem Fall stärker als bei der einfachen war“, berichtet Zaretskaya. Die ProbandInnen wurden auch gefragt, für welche Variante sie sich intensiver konzentrieren mussten, um sie zu erkennen. „Es zeigte sich, dass die Aktivität im IPS vom Grad der Konzentration unabhängig ist“, ergänzt die Wissenschafterin. „Da alle drei voneinander verschiedenen Stimuli dasselbe Ergebnis liefern, ist dies ein Hinweis darauf, dass das Aktivierungsmuster im IPS einen allgemeingültigen Mechanismus für die Gestaltwahrnehmung darstellen könnte“, fasst Pablo Grassi die bedeutenden Erkenntnisse zusammen.

Publikation: Pablo R. Grassi, Natalia Zaretskaya, Andreas Bartels (2018): A Generic Mechanism for Perceptual Organization in the Parietal Cortex. Journal of Neuroscience 13 July 2018, 0436-18.
www.jneurosci.org/content/early/2018/07/13/JNEUROSCI.0436-18.2018

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

(Text: Mareike Kardinal, HIH)

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen
• Hertie Institute for Clinical Brain Research
• Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
• Bernstein Center for Computational Neuroscience
• Max Planck Institute for Biological Cybernetics
• Max Planck Institute for Intelligent Systems

At a glance, it would seem that the glassily-transparent, millimeter-long larva of a popular ornamental fish from South Asia has very little in common with a human being. Nevertheless, in recent years zebrafish have risen to popularity as one of the most widely used object of study with researchers interested in the basic mechanisms of perception. One example among many is eye motor control: when they move their eyes to follow mobile visual stimuli, zebrafish employ mechanisms very similar to those in the human visual system.

But in order to see how a fish sees, researchers must invest in extremely elaborate laboratory equipment – a fact of life in much of life science. One important component of this equipment is the software solutions to obtain and measure the numerous parameters the researchers are looking for. Quite often, they face a sort of agony of choice here: on one hand, they could use commercially available software, which rarely does precisely what a given research group needs for their specific angle of investigation. Moreover, such commercial solutions for tracking eye movements in fish are available only at great expense. On the other hand, the lab group could program their own applications ‒ besides requiring good programming skills, this often takes years of dedicated work.

When neurobiologist Aristides Arrenberg faced this dilemma during his years as a doctoral student, he decided to develop his own software suited to his project’s needs. Today he heads a research group at the CIN in Tübingen, which still uses a version of this software, retooled and expanded over the years. By now it has picked up a lot of additional functionality, being able to control individually tailored light stimuli presented to fish larvae, and to automatically register, track and record their eye movements, even perform real-time analyses. On top of that, there are plugins for laser and microscope usage, as well as a graphical user interface optimized for ease of use. The researchers have decided to make their software – which they call ‘ZebEyeTrack’ – freely available to all laboratories studying the visual system of zebrafish.

"Naturally, researchers worldwide have very specific requirements for their software solutions. For this reason we are sharing the source code, so that anybody with a little programming skill can adapt it to their individual needs", explains Florian Dehmelt, who programmed the (for now) final version. Research group leader Arrenberg adds: "With ZebEyeTrack, we are part of the Open Source movement. We could probably have filed for a patent and sold ZebEyeTrack commercially. But we are not interested in doing so – after all, we would be continuing the very same problem that got us started in the first place.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Systems Neurobiology

Contact: Jun.-Prof. Dr. Aristides Arrenberg

Dancing, shaking hands, playing ballgames – all activities of this kind rely on interconnected action pairs of at least two persons, such as „giving and taking“ or „throwing and catching“. How does the brain process interactions in which the actions of several individuals are interrelated? Do we recognise interactions such as these by correlating the individual partners’ motions on a very basic, perception-based level? Or do we first analyse their actions cognitively and attribute a meaning to them?

A collaborative study of neuroscientists belonging to the Tübingen Max Planck Institute for Biological Cybernetics (MPI BC), the Hertie Institute for Clinical Brain Research (HIH) and the Werner Reichardt Centre for Integrative Neuroscience (CIN) has tackled these questions. The researchers utilised of a virtual reality environment, in which a life-sized three-dimensional animated avatar performed various actions: some clearly recognisable as parts of an action pair, others action mixes in between. The researchers exploited an adaptation effect: unclear stimuli will be differently interpreted based on what stimuli had been in effect earlier. For instance, if probands are repeatedly shown a “giving” gesture and are subsequently confronted with an unclear mix of a “giving” and “throwing”, they will interpret the action mix as “throwing” in the majority of trials.

The researchers were intrigued to not only find this adaptation effect with regard to the first part of a social action sequence, such as “giving”, or “throwing”. The effect also occurred when the matching second part of the sequence was shown first: “taking” or “catching” in these instances. It appears that the very neurons responsible for representing “giving” also respond to its matching opposite “taking”. The action pair “giving-taking” is represented as one unit in the brain. Further control experiments showed that only those actions which are part of a matching pair will trigger the above-mentioned adaptation effect, while completely different actions such as “dancing” will not.

“In the human brain, giving and taking are represented together”, affirms Stephan de la Rosa from the MPI for Biological Cybernetic, who conceived the study and performed the experiments together with Leonid Fedorov (HIH/CIN). “Our results show that there are neurons that very likely respond similarly to both halves of an action pair”, says Fedorov’s supervisor Martin Giese (HIH/CIN). Concerning the impact of their findings, the authors are optimistic: “In many autistic disorders, the perception of social interactions such as those we have investigated here is impaired. We believe that our results may be an important step on the way to a better understanding of these socio-cognitive disorders.”

Organization:

• Max Planck Institute for Biological Cybernetics
• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Computational Sensomotorics

Contact: Prof. Dr. Martin A. Giese

How do we know what happened to us yesterday, or last year? How do we recognize places we have been, people we have met? Our sense of past, which is always coupled with recognition of what is currently present, is probably the most important building block of our identity. Moreover, from not being late for work because we could not remember where the office was, to knowing who our friends and family are, long-term memory is what keeps us functional in our daily lives.

It is therefore not surprising that our brain relies on some very stable representations to form long-term memories. One example are memories of places we have seen. To each new place, our brain matches a subset of neurons in the hippocampus (a centrally located brain area crucial to memory formation): place cells. The memory of a given environment is thought to be stored as a specific combination of place-cell activity in the hippocampus: the place map. Place maps remain stable as long as we are in the same environment, but reorganize their activity patterns in different locations, creating a new place map for each environment.

To date, the mechanisms which underlie this reorganization of place cell activity have remained largely unexplored. In 2016, Tübingen neuroscientists headed by Dr Andrea Burgalossi had shown that silent, dormant cells can be activated by electrical stimulation and become active place cells in the rat brain. Building upon this work, the team has continued investigating the ways place cells are formed and have now presented evidence that place cells are not nearly as stable as had been thought: they can, in fact, even be ‘reprogrammed’.

The setup, which is unique in the world, uses juxtacellular recording and stimulation – a method where a hair-fine electrode measures and induces the tiny currents along individual place cells – in live animals freely roaming an arena in the lab. With this setup, the researchers targeted individual place cells in a mouse’s brain and stimulated them in a different location from where they had originally been active. In a significant number of cases, they found that the activity of the place cells could be ‘reprogrammed’: the cells stopped firing in the original locations, and became active in the area where the electrical stimulation was delivered. In other words, the reprogrammed place cells would, from now on, become active whenever the mouse wandered to the stimulus location, but remain silent in the old location.

“We challenged the idea that place cells are stable entities. Even in the same environment, we can reprogram individual neurons by stimulating them at specific places”, says Andrea Burgalossi. “This finding provides insights into the basic mechanisms that lead to the formation of new memories”. In the near future, the scientists hope to be able to reprogram multiple neurons simultaneously, so to test the plasticity of place maps as a whole. “So far, we have reprogrammed single neurons, and it would be fascinating to find what influence this has on place maps as a whole. We would very much like to know what is the minimum number of cells we need to reprogram in order to modify an actual memory trace in the brain.”

Publication:
Maria Diamantaki, Stefano Coletta, Khaled Nasr, Roxana Zeraati, Sohie Laturnus, Philipp Berens, Patricia Preston-Ferrer, Andrea Burgalossi: Manipulating Hippocampal Cell Activity by Single-Cell Stimulation in Freely-Moving Mice. In: Cell Reports (in press) April 3rd, 2018.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neural Circuits and Behavior

Contact: Dr. Andrea Burgalossi

Even while we move through it, our environment looks stable to us, because the brain constantly balances input from different senses. Visual stimuli are compared with, and corrected for input from our sense of equilibrium, of the relative positions of our head and body, and of the movements we are performing. The result: when we walk or run around, our perception of the world surrounding us does not roll our bounce. But when visual stimuli and our perception of movement do not fit together, this balancing act in the brain falls apart.

Anybody who has ever delved into fantasy worlds with virtual reality glasses may have experienced this disconnect. VR glasses continually monitor head movements, and the computer adapts the devices’ visual input. Nevertheless, prolonged use of VR glasses often leads to motion sickness: even modern VR systems lack the precision necessary for visual information and head movements to chime perfectly.

Up to now, neuroscientists have not been able to identify the mechanisms that enable the brain to harmonise visual and motion perception. Modern noninvasive studies on human subjects such as by functional magnetic resonance imaging (fMRI) run into one particular problem: images can only be obtained of the resting head.

Two Tübingen neuroscientists, Andreas Schindler and Andreas Bartels, have developed a sophisticated apparatus to circumvent this problem. They are now able to employ fMRI to observe what happens in the brain when we move our head while perceiving fitting – or non-fitting – visual and motion stimuli. In order to do so, subjects wearing VR glasses entered a specially modified fMRI scanner. In this scanner, computer-controlled air cushions quickly fixated the probands’ heads immediately following movement. During the head movements, the VR glasses displayed images that were were congruent with the movements. In other cases, the glasses displayed images incongruent with head movements. Right when the air cushions had stabilised the probands’ heads after the movements, the fMRI signal was recorded.

Andreas Schindler explains the procedure: “With fMRI, we cannot directly measure neuronal activity. fMRI just shows blood flow and oxygen saturation in the brain, with a delay of several seconds. That is often seen as a deficiency, but for our study, it was actually useful for once: we were able to record the very moment when the subject’s brain was busy balancing its own head movement and the images displayed on the VR glasses. And we were able to do so seconds after the fact, when the subject’s head was already resting quietly on its air cushion. Normally, head movements and brain imaging don’t go together, but we hacked the system, so to speak.”

In this way, the researchers could observe in the healthy human brain that which had so far only been investigated in primates and, indirectly, in certain patients with brain lesions. Their result: one area in the posterior insular cortex showed heightened activity whenever the VR display and head movements congruently simulated a stable environment. When the two signals conflicted, this heightened activity vanished. The same observation held true in a number of other brain regions reponsible for the processing of visual information in motion.

The new method and results open the door for a more focused study of the neuronal interactions between motion and visual perception. Moreover, the Tübingen researchers have shown for the first time what happens in the brain when we enter virtual worlds and balance on the knife’s edge between immersion and motion sickness.

Publication:
Andreas Schindler, Andreas Bartels: Integration of Visual and Non-Visual Self-Motion Cues during Voluntary Head Movements in the Human Brain. In: NeuroImage 172. S. 597–607. 15. Mai 2018 (online publication ahead of print). doi: 10.1016/j.neuroimage.2018.02.006

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Max Planck Institute for Biological Cybernetics

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

It sounds like science fiction: we can alter the human brain’s activity simply by holding a wire coil over the head, resulting in movement of the arms or legs. This technique is called transcranial magnetic stimulation (TMS), and it is much used in research and medicine. In TMS, a strong magnetic pulse induces tiny electrical currents in the affected brain tissue. These currents can activate nerve cells.

In medicine, TMS is used to diagnose impairments of motor function such as in multiple sclerosis or as a result of a stroke. TMS is also used therapeutically, for instance to treat tinnitus, clinical depression, chronic pain or addictions. In Europe, however, TMS is not yet an established method of treatment.

This is partly because researchers still do not really understand what happens on a neuronal level when the magnet is switched on – even though TMS has been under investigation for more than 30 years. This lack of understanding is due to the fact that neuronal activity in the brain is usually recorded with microelectrodes. But such recordings are massively disturbed by the strong magnetic fields brought to bear in TMS, resulting in masked signals from the neurons’ activity.

Now researchers from several groups (Cornelius Schwarz, Martin Giese, Ulf Ziemann and Axel Oeltermann) at three Tübingen institutes (Werner Reichardt Centre for Integrative Neuroscience, Hertie Institute for Clinical Brain Research, and Max Planck Institute for Biological Cybernetics) have cooperatively developed a method to shield microelectrodes against TMS-induced magnetic fields. In this way, they can detect changes in individual brain cells with a delay of only one millisecond after the magnetic pulse.

In their study, the Tübingen researchers show how reliable data can be acquired using their shielding technique. In rats, they stimulated the part of the motor cortex that controls forelimb movement. While the rats moved their forepaws following the magnetic stimulation, the researchers measured their neuronal activity. Observing the cortex neurons’ activity directly under TMS, they found that this activity remained for some time after the TMS pulse had ended. Furthermore, the direction of TMS-induced electrical currents in the brain influenced the neuronal activity detected by the researchers. These findings fit with prior experiments done in human subjects, where neuronal activity in the spine and the muscles was measured instead of the brain.

“There are only two research groups in the world who have done something like this”, says Dr. Alia Benali, who planned and performed the study. The methods employed by these two groups, however, require exceedingly demanding engineering capabilities. Moreover, they have been developed specifically for primate brains. Because of these restrictions, many laboratories will not be able to make use of these methods. “We wanted to develop a simple method to investigate neuronal activity under TMS. Any given lab should be able to use it without specific know-how”, PhD student Bingshuo Li explains.

Publication:
Bingshuo Li, Juha P. Virtanen, Axel Oeltermann, Cornelius Schwarz, Martin A. Giese, Ulf Ziemann, Alia Benali: Lifting the Veil on the Dynamics of Neuronal Activities Evoked by Transcranial Magnetic Stimulation. eLife 2017;6:e30552; DOI: 10.775/eLife.30552

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research
• Max Planck Institute for Biological Cybernetics

Reseach Group: Systems Neurophysiology

The photoreceptors in the retina, at the back of the eyes, are the primary light sensitive cells that allow us to see: they convert light into electrical signals. There are two types, rods and cones, and it has generally been assumed that rods are responsible for seeing in dim light conditions, whereas cones allow vision in bright light. This division of labor between rods and cones can be found in virtually every biological and medical text book.

A new study challenges this traditional view: A group of researchers from the universities of Tübingen, Manchester and Helsinki led by Thomas Münch from Tübingen shows that rod photoreceptors do, in fact, contribute to daylight vision. Most surprisingly, their contribution even increases when the daylight becomes brighter, up to the brightest light levels that would ever be encountered in natural environs.

Using transgenic mice without functional cones, the investigators first measured rod-driven signals and could reliably detect them both in the retina and in the brain even at high light levels. Furthermore, they were subsequently able to show this bright-light rod contribution in mice with fully functional cones as well.

With this new data, it seemed obvious that the models used by most scientists beforehand must be incomplete. And indeed, much was already known about rod physiology that had not been included in the big picture, as it has been understood up to now. Adding this information, the research team arrived at a model that not only explains how rods see so well in dim light, but also their own findings: that rods continue to function in bright light.

“We showed that rods can function at bright light”, says Thomas Münch, “but it is true that cones can do this much better and much more reliably. However, these new insights may still open new avenues towards treatments for patients without functional cones, so-called rod monochromats.” People in modern times are exposed to artificial bright light for many hours each day. In the old paradigm, this has made reliance on rods for the development of treatments counterintuitive. With these new mechanistic insights into bright rod vision, however, there may be new possibilities for therapies for patients without functional cone vision.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Retinal Circuits and Optogenetics

Patricia Preston-Ferrer vom Werner Reichardt Centrum für Integrative Neurowissenschaften (CIN) der Universität Tübingen hat „einen wichtigen Meilenstein in der Ausarbeitung des Raumgedächtnisses“ geliefert, so die Begründung der Jury. Sie befasste sich in ihrer Arbeit mit der Frage, wie das Gehirn eine Orientierung im Raum möglich macht. Dafür untersuchte sie sogenannte Kopfrichtungszellen in Nagetiergehirnen. Das sind Neuronen, die die Ausrichtung des Kopfes erkennen. Bisher wurde zwar vermutet, dass diese Zelltypen existieren, ihre genaue Lage im Gehirn war allerdings nicht eindeutig geklärt. Mit neuen Methoden machte Preston-Ferrer diese Neuronen im Gehirn erstmals sichtbar. Außerdem zeigte sie, wie Kopfrichtungszellen mit anderen Gehirnarealen verbunden sind. Preston-Ferrer konnte erstmals eine Verbindung zwischen Struktur und Funktion der Kopfrichtungszellen herstellen und trägt damit maßgeblich zum Verständnis des Orientierungssinns bei. Möglicherweise wird sich ihre Arbeit als wichtiger Impuls für die Erforschung der Alzheimerkrankheit erweisen, bei der der Verlust des Orientierungssinns als eines der ersten Symptome gilt. Die Ergebnisse wurden in der Zeitschrift eLife veröffentlicht.

Sarah Wiethoff vom Hertie-Institut für klinische Hirnforschung (HIH) wird ausgezeichnet für ihre Untersuchung über die seltene Krankheit der erblichen spastischen Para­plegie. Die Ursachen für die Krankheit liegen im Gehirn und in den Nerven, die vom Gehirn zum Rückenmark laufen. Bei Patienten, die davon betroffen sind, versteift sich vor allem die Beinmuskulatur, so dass sie je nach Schweregrad und Fortschreiten der Krankheit auf den Rollstuhl angewiesen sein können. In einer klinischen Studie untersuchte Wiethoff die Krankheitsverläufe von über 600 Betroffenen. Erstmals hat sie in zeitintensiver Kleinarbeit das vielschichtige Krankheitsbild dokumentiert. Dafür kooperierte sie mit mehreren Einrichtungen, erstellte detaillierte individuelle Krankheitsprofile und ordnete bestimmte Beschwerden, zum Beispiel Krampfanfälle, verschiedenen genetischen Defekten zu. Ihre Arbeit trägt dazu bei, dass Ärzte ihren Patientinnen und Patienten künftig genauere Prognosen zum Krankheitsverlauf der erblichen spastischen Paraplegie geben können. Außerdem ist die Arbeit, die in den Annals of Neurology veröffentlicht wurde, Grundlage für künftige Therapiestudien.

Die Preisverleihung findet statt am Mittwoch, den 18. Oktober 2017, um 14.30 Uhr im Großen Senat der Neuen Aula (Geschwister-Scholl-Platz, 72074 Tübingen) zu Beginn der Mitgliederversammlung des Universitätsbundes. Medienvertreterinnen und Medienvertreter sind herzlich eingeladen.

Der Attempto-Preis wurde 1983 von dem Psychiater Konrad Ernst und seiner Ehefrau Dorothea gestiftet. Er wird jährlich an Nachwuchswissenschaftlerinnen und -wissenschaftler für herausragende Arbeiten über Hirnleistungen und deren Störungen vergeben, die an der Universität Tübingen und an den der Universität verbundenen Tübinger Einrichtungen der Max-Planck-Gesellschaft entstanden sind. Zurzeit werden jährlich zwei Nachwuchswissenschaftlerinnen oder Nachwuchswissenschaftler mit einem Preisgeld in Höhe von je 10.000 Euro ausgezeichnet. Das Geld kann zur Förderung ihrer weiteren wissenschaftlichen Karriere eingesetzt werden.

Porträtbilder der Preisträgerinnen zum Download unter www.pressefotos.uni-tuebingen.de/20171012_Attempto-Preis.zip - Fotos: Friedhelm Albrecht/Universität Tübingen

Publikationen:
Preston-Ferrer P, Coletta S, Frey M, Burgalossi A (2016): Anatomical organization of presubicular head-direction circuits. eLife, pii:e14592.
Schüle R*, Wiethoff S*, Martus P, Karle K, Otto S, Klebe S, et al. (2016): Hereditary spastic paraplegia – clinicogenetic lessons from 608 patients. Annals of Neurology, 79(4), S.646-658.
*These authors contributed equally.

Organization:

• University of Tübingen
• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Neural Circuits and Behavior

–– this press release is reproduced here with kind permission of the Ernst Schering Foundation ––

Ivana Nikić-Spiegel is group leader at the Werner Reichardt Centre for Integrative Neuroscience of the University of Tübingen. In her research, she combines two state-of-the-art technologies in a promising way. Already in her doctoral work at the University of Munich (LMU), the molecular biologist was able to describe a new form of neuronal damage (the so-called focal axonal degeneration), which is caused by immune cell attacks. But what happens at the molecular level during this neuronal damage? As a post-doc at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Ivana Nikić-Spiegel developed a new method for protein labeling. Combining this with the use of super-resolution microscopy, she is now able to image the function of proteins at nanometer resolution and to use this technique for her investigations into neuroinflammation.

For her outstanding research Dr. Ivana Nikić-Spiegel is awarded with this year’s Friedmund Neumann Prize. The Ernst Schering Foundation awards the 10,000-euro prize to young scientists who have done outstanding basic research in human biology, organic chemistry or human medicine and who have already developed a distinctive scientific profile since completing their dissertation. The award aims to make visible excellent scientific achievement and help young scientists establish themselves in their field of research.

Dr. Nikić-Spiegel was nominated for the Friedmund Neumann Prize 2017 by Dr. Edward Lemke, group leader at the EMBL. “Ivana Nikić-Spiegel’s research helps us understand the pathology of multiple sclerosis, from the molecular all the way to the physiological and medically relevant levels. At the same time, she has the unique ability to develop and apply new and groundbreaking tools of chemical biology. This makes her research truly cutting-edge and internationally outstanding,” says Lemke.

Award Ceremony Friedmund Neumann Prize
September 25, 2017, 6:30 p.m.
Leibnizsaal at the Berlin-Brandenburg Academy of Sciences and Humanities
Markgrafenstr. 38 | 10117 Berlin
Registration is possible until September 17 at anmeldungspam prevention@scheringstiftung.de

The award ceremony features a musical performance by the STEGREIF.orchester. It is the only improvised symphony orchestra worldwide, consisting of 24 young musicians who want to revolutionize classical music. Breaking away from strict conventions, they use neither sheet music nor a conductor. The resulting freedom facilitates spontaneity, improvisation, and movement. Each production is based on a classical symphony which is combined with different musical styles such as jazz, folk or techno. The STEGREIF.orchester thus creates a completely new sound experience, which is supported by an expressive choreography. www.stegreif-orchester.de

On the occasion of the award presentation, Dr. Ivana Nikić-Spiegel will present and discuss her research with students of the Lise Meitner School in Berlin on September 26.

Background information

Multiple sclerosis (MS) is a common neuroinflammatory disease, in which immune cells attack components of the central nervous system. These inflammatory attacks can happen at almost any region in the brain and spinal cord leading to a number of neurological symptoms, such as vision disturbances, numbness, tingling, mobility problems, fatigue and pain. Symptoms differ from patient to patient and MS has an unpredictable but often disabling course. It affects around 2.5 million people worldwide, of which more than 120,000 patients live in Germany. Current therapies cannot stop the progression of the disease. Consequently, it is important to understand the disease mechanisms.
During her PhD at the LMU, Ivana Nikić-Spiegel was trying to understand how immune cells damage axons – the long projections of neuronal cells. Axons are crucial for information transfer in the brain, and axonal injury is largely responsible for the irreversible neurological deficits that MS patients acquire. With transgenic mice and a special type of microscopy, she could directly look at the interaction of immune cells and axons. As a result of her PhD, Ivana Nikić-Spiegel and her colleagues described a new form of axonal injury. In a mouse model of multiple sclerosis, they could even reverse some of these damages. However, to translate their therapeutic approach from a mouse model into a real therapy of benefit for patients, scientists need to further understand what is happening at the molecular level. This is what Ivana Nikić-Spiegel’s group is currently doing. With a special type of light microscopy with nanometer ("super") resolution and new methods for protein labeling that Ivana Nikić-Spiegel developed during her postdoctoral work, Ivana Nikić-Spiegel and her team want to peer deeper inside the damaged axons. By combining these cutting-edge techniques, they hope to advance the molecular understanding of multiple sclerosis which might define new therapeutic targets.

Ivana Nikić-Spiegel studied molecular biology and physiology at the University of Belgrade in Serbia. Afterwards, she moved to Munich to join the laboratory of Martin Kerschensteiner at the University of Munich (LMU) where she did her PhD. Her PhD thesis was co-supervised by Thomas Misgeld from the Technical University of Munich (TUM). After her PhD, for which she won the “Dr. Hildegard und Heinrich Fuchs Preis zur Förderung medizinischen Nachwuchses” – the award for the best thesis in the Medical Faculty at the LMU – Ivana Nikić-Spiegel joined the Lemke group at the EMBL in Heidelberg. During her postdoctoral training she was supported by a Marie Curie IntraEuropean and an EMBO long-term fellowship. After her postdoc, she was appointed as a junior group leader at the Werner Reichardt Centre for Integrative Neuroscience in Tübingen. Last year Ivana Nikić-Spiegel got accepted in the Emmy Noether program of the DFG which will provide a 5-year support in research funds for her research group.

More information and images are available for download at www.scheringstiftung.de in the “press” section.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

In modern neuroscience, small animals provide insights into basic functions of the nervous system. The translucent larvae of zebrafish, the fruit fly Drosophila, or the tiny nematode (roundworm) Caenorhabditis elegans are easy to keep in large numbers. More importantly, their genomes have been completely sequenced, allowing many modifications, such as for optogenetics. With this technique nerve cells are genetically programmed to react to light, so brain areas or even individual nerve cells can in effect be “switched on” or “off” – in the live organism. This allows specific identifications of the nerve cells responsible for controlling specific functions and behaviours. The intricate equipment necessary for these experiments includes light sources with defined wavelengths and adjustable intensities; powerful cameras and microscopes; and a custom-tailored so-called “arena” for behavioural studies of live specimens. A lab can easily spend tens to even hundreds of thousands of Euros on commercially available solutions, confining top-level research and scientific training to well-endowed institutes in rich countries.

In a joint initiative, neuroscientists of the Tübingen Werner Reichardt Centre for Integrative Neuroscience (CIN) and Institute for Ophthalmic Research and the University of Sussex in Brighton have now presented the “FlyPi”. The design is based on a 3-D printed framework holding a Raspberry Pi computer and camera, cheap LEDs for lighting and simple lenses, as well as optical and thermal control circuits based on Arduino, an open-source electronic prototyping platform. Taken together, the components cost less than 100 Euros for the basic system, which can carry many add-on modules which still merely double the total. Commercially available solutions are obviously more sophisticated in some aspects. For example, spatial resolution in fluorescence microscopy ranges in the micrometers, where state-of-the-art confocal or 2-photon microscopes reach tenths of micrometers. But this factor of ten in spatial resolution compares well to a factor of up to 5,000 in cost. The FlyPi performs very well in many standard tasks needed in neuroscience labs on a day-to-day basis and is more than adequate for teaching purposes. Due to its modular nature, it can be fitted with more costly components to improve certain performance aspects – spatial resolution, for example.

The developers of the FlyPi system, André Maia Chagas and Tom Baden, share a keen interest in spreading “open labware”. That is what the growing community of scientists interested in open source, DIY engineering and gadgeteering calls projects such as this. For years now, and together with co-author Lucia Prieto Godino of the University of Lausanne, the two scientists have taught courses in 3 D printing, programming and DIY lab equipment at universities in Kenya, Uganda, Ghana, Nigeria, South Africa, Sudan and Tanzania. “These institutions have little money to spend on costly equipment”, says Baden. “We think it is very important that neuroscientific training and research open up to larger numbers of students and junior scientists in these developing countries. So we hope that, with open labware such as our FlyPi, we can offer a starting point.”

Publication:
André Maia Chagas, Lucia Prieto Godino, Aristides B. Arrenberg, Tom Baden: The 100 Euro Lab: A 3-D Printable Open Source Platform for Fluorescence Microscopy, Optogenetics and Accurate Temperature Control during Behaviour of Zebrafish, Drosophila and C. Elegans. PLoS Biology 18 July 2017.
doi.org/10.1371/journal.pbio.2002702

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

We ceaselessly sense our surroundings: we hear, feel, smell and taste it. Yet the dominant factor feeding our view of the world is the way we see it. How does information about our visual surroundings, projected into our eyes as patterns of light, enter our brain to create our internal representation of the world? Seeing is not as simple as assembling an image from many individual dots, like a digital photo. Our visual system processes information using many channels simultaneously, literally creating a multi-layered ‘bigger picture’. The very first level of the visual system, the retina, already provides information on colour, contrast, movement, and brightness. We notice individual objects ‘at a glance’ because they jump out from what we see as mere background. Moving stimuli likewise command immediate attention.

For visual information to reach the brain through such parallel channels, images are pre-processed in the retina. For years, a team of scientists led by Prof. Thomas Euler (CIN – Werner Reichardt Centre for Integrative Neuroscience & Institute for Ophthalmic Research at the University of Tübingen) has been investigating the retinal ‘switchboard’ responsible for much of this processing. Recently, they focused on bipolar cells. Bipolar cells link the light-sensitive photoreceptor cells in the eye with retinal ganglion cells, which in turn forward the retinal output to the brain. Genetically and anatomically, 14 different types of bipolar cells have been identified. The Tübingen researchers therefore tested the hypothesis that each of these 14 cell types represents one visual channel, each with its own function. But how are these channels different from each other, and what are the mechanisms involved?

To answer this question, the scientists projected many different patterns of light onto mouse retinas. Simultaneously, they made use of a genetically encoded fluorescent protein to measure bipolar cell output. With this method, they were able to take measurements from a very large number of individual synapses (more than 13,000), and from all types of bipolar cells.The results showed one surprising fact: when subjected to small spots of light, the 14 bipolar cell types’ functions seemed very similar. Only larger stimuli covering far more than one cell’s receptive field – the area where a bipolar cell collects photoreceptor inputs – generated different signals across multiple channels. Further experimentation showed that the bipolar cells’ neighbours, so-called amacrine cells, are responsible for this diversification of encoded information.

Katrin Franke, who designed the study and performed the experiments, explains the findings like this: ‘Instead of simply telling the brain “in my receptive field, it is currently bright/dark/green/blue”, bipolar cells that receive input from amacrine cells can tell the brain more detailed information, like “it is bright here, but right next to where I am, it is dark”. This level of detail allows the brain to assemble a complex layered impression including transitions, contrast, edges and movement.’

A better understanding of signal processing in the retina may be beneficial not only for basic research, but also in eye care medicine. For several years now, a retina implant for patients with degenerative eye conditions has been under development at the University of Tübingen’s eye clinic. This implant makes use of bipolar cells, as these form the second layer downstream of photoreceptor cells lost to the progress of disease. Accordingly, the new study’s insights promise to promote further application-oriented research in the field.

Publication:
Katrin Franke, Philipp Berens, Timm Schubert, Matthias Bethge, Thomas Euler, Tom Baden: Inhibition Decorrelates Visual Feature Representations in the Inner Retina. Nature (in press). February 8th, 2017.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

This is what happened at Dr. Steffen Hage’s research group at the Tübingen Werner Reichardt Centre for Integrative Neuroscience (CIN): the main focus of the scientists is to investigate vocal motor production and cognitive control mechanisms in the brain. To this end, they also conduct behavioural experiments with marmoset monkeys. These animals, barely larger than a squirrel, are especially suited for this kind of research, since they are a loquacious species that communicates with their fellows in a complex manner.

One of the marmoset couples had a litter of three infants, one of which the parents rejected. Since common marmosets usually give birth to twins, and parents are not able to fully care for three young in most cases, it is quite common that the third infant is rejected by its parents. This third animal was hand-fed by an animal caretaker at the CIN. However, marmosets are communal animals that need stable social groups. Therefore the researchers wanted to reunify the rejected infant with its siblings as soon as possible. After three months’ time, the young remaining with their parents had been weaned, and the three monkey siblings were brought together again. The resulting social group has proven stable. By now, the animals are fully grown up.

After a few weeks had passed, Yasemin Gültekin, a PhD student from Hage’s team, noticed an interesting peculiarity: the three siblings still made typical baby monkey noises, so-called “babbling”. Normally, marmosets only show this vocal behaviour during the very first months after birth. At first the researchers assumed they would grow out of it, but even while the siblings added adult calls to their repertoire, the rapidly growing monkeys retained the “babbling”, too. They still employ both now, as Gültekin & Hage’s detailed records show. Hage concludes that “apparently, the animals need direct social or acoustic feedback from their parents for normal development of their vocal behaviour”.

Hage’s team had in fact been expecting marmoset vocalisation to be completely innate, i.e. the basic pattern of calls usually develops without acoustic feedback. Intrigued, the neuroscientists investigated further. When the parent monkeys had offspring a second time – twins this time –, they quickly brought their microphones to bear. The second litter, which, as is the usual practice, were kept with the parents far longer than three months, developed vocalisations according to what the researchers had expected in marmosets. At about seven months of age, they showed no infant vocalisations anymore, only adult call types. Comparing the total of almost 14,000 individual calls on record for the five siblings, there is conclusive evidence: while marmosets may not learn twittering, pheeing and peeping from their parents, they apparently do learn what you can “say” when and where as an adult.

Hage and his team are very happy with their results: “The vocal behavior of marmosets is different from that of humans or e.g. songbirds, since monkeys are not capable of learning new acoustic structures. However, it seems that developing the repertoire available to them heavily depends on direct feedback mechanisms much like our own. These animals are a compelling model system to investigate such early vocal development in humans. We can therefore learn a lot about early vocal development in humans from these animals.”

Yasemin B. Gultekin, Steffen R. Hage (2016): Limiting Parental Feedback Disrupts Vocal Development in Marmoset Monkeys. Nature Communications 8: 14046.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neurobiology of Social Communication

Contact: PD Dr. Steffen Hage

"Currently, signal processing in the brain can be measured by various methods," Scheffler explains. The so-called electrophysiology, for example, allows a very detailed recording of local events, because nerve cells in the brain communicate with each other by means of electrical signals. To measure this activity, a hairy microelectrode is placed in the cerebral cortex or deeper brain structures. Thus the signal of a small number or even a single nerve cell can be observed. Electrophysiology is often used in neurosciences in animal experiments, but also in medicine, for example during brain surgeries.

Magnetic resonance imaging, on the other hand, is a non-invasive method with a very high spatial resolution in the millimeter range and the possibility of detecting the entire brain in humans or animals. Magnetic resonance is often presented as an alternative method to invasive methods, but unlike electrophysiological recordings it cannot directly measure neuronal activity. Research is therefore done with a methodical detour: Magnetic resonance imaging allows to detect local changes in the blood oxygen content in the brain, which in turn is modulated by the neuronal activity.

"This so-called neurovascular coupling is not fully understood at this time," Scheffler says, "a prediction of the underlying neuronal activity of the brain based on functional MRI data is therefore very difficult if not impossible." The newly approved Koselleck project therefore has its goal to better understand the relationship between vascular and neural signals. In this project, novel magnetic resonance methods are being investigated with the aim of obtaining more detailed information on the underlying neuronal activities. For this purpose, it is important to know the exact anatomy of the neural vascular system, which is measured by experiments with high-resolution MicroCT. All in all, the approved Koselleck project aims to provide a more accurate picture of the neuronal interactions of the entire brain as a system.

Koselleck projects of the DFG represent particularly innovative and, in the positive sense, risk-related research. Scientists, who have shown special scientific achievements, are given the opportunity to carry out highly innovative and positively risky projects. The funding line is named after Reinhart Koselleck, who died in 2006, one of the most important German historians of the 20th century, one of the founders of modern social history.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Max Planck Institute for Biological Cybernetics

Reseach Group: Biomedical Magnetic Resonance

Contact: Prof. Dr. Klaus Scheffler

Many things we think we know about the world have their origin in popular culture, not science. The most well-known false ‘fact’ about the brain is the misconception that we only use ten percent of the brain’s overall capacity. This so-called ’ten percent myth’, while accepted as such by neuroscientists, still regularly figures in advertisement, but also in books and short stories as well as films. As with any myth, however, there is a kernel of truth at the core of the matter: many neurons remain dormant for most if not all of our life, even while their direct neighbours show regular activity.

A team of neuroscientists led by Dr. Andrea Burgalossi of the Werner Reichardt Centre for Integrative Neuroscience (CIN) at the University of Tübingen have now taken an important step towards understanding why some neurons are active and others are not: they can tell them apart morphologically. To be able to do so, the investigators employed so-called juxtacellular recordings in freely-moving rats. With this technique, electrodes are inserted right next to individual, functioning neurons in live organisms. This allows recording action potentials from these neurons while they work, and while simultaneously identifying the cells that the recordings are taken from for later analysis.

During this analysis, morphological traits of the analysed cells are identified, most importantly their dendritic arbors, i.e. the filament structures which receive input signals from other neurons. The cells under investigation were granule cells (GCs) in the rat’s dentate gyrus (DG). Dentate GCs have been shown to be intimately connected to individual memories of places and individuals, and thus playing a central role in memory tasks.

The researchers recorded from 190 GCs, only 27 of which they found to be active (ca. 14 percent). While this seems to give credibility to the ‘ten percent myth’, the team actually expected this outcome, as the DG is a brain structure where in any given task, only a very small percentage of neurons take part, while their neighbours remain dormant, waiting for their ‘cue’, as it were. Memory functions in the brain work according to a principle that neuroscientists call ‘sparse coding’, i.e. a comparatively small number of neurons encode complex information – possibly to make overlap between different memories more unlikely.

Using a smaller subsample, the scientists looked for correlations between active and passive functionality and the respective cells’ morphology. Their results show that active GCs have much more complex dendritic arbors. They not only transfer and receive information from many more neurons than the inactive ones, they also have better cellular ‘infrastructure’ to do so. Despite their as of yet limited sampling, the scientists are positive that they can now tell apart active and inactive GCs, mostly by merely looking at them. “Explaining the causes of activity in some and inactivity in other neurons may still take a long time”, cautions Burgalossi, leader of the research group. “But finding a direct link between function and morphology is an important step forward. It will be even more challenging to find evidence of causality. But we are on the right track.”

Publication:
Maria Diamantaki, Markus Frey, Philipp Berens, Patricia Preston-Ferrer, Andrea Burgalossi: Sparse Activity of Identified Dentate Granule Cells during Spatial Exploration. eLife. 3 October 2016. pii: e20252.
elifesciences.org/content/5/e20252

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neural Circuits and Behavior

Contact: Dr. Andrea Burgalossi

„Bislang war nicht bekannt, wie Kausalitätsurteile auf der Ebene von Nervenzellen verarbeitet werden“, erklärt Martin Giese. „Man vermutete jedoch einen Zusammenhang mit der Verarbeitung von motorischen Handlungen – in beiden Fällen muss das Gehirn räumlich-zeitliche Zusammenhänge zwischen Reizen auswerten, die sich gegenseitig beeinflussen.“

In ihrer Studie maßen die Wissenschaftler die Aktivität der Spiegelneurone in der motorischen Hirnrinde von Makaken. Während des Experiments wurden den Tieren auf einem Bildschirm natürliche Handbewegungen sowie abstrakte Reize in Form von bewegten Scheiben gezeigt. Der Bewegungsverlauf der Hände und Scheiben wird durch die gleichen kausalen Beziehungen beschrieben. Es zeigte sich: Die Aktivitätsmuster der Spiegelneurone waren für beide Reizarten fast identisch. „Das Ergebnis deutet darauf hin, dass motorische Bewegungen und bestimmte Aspekte visueller Kausalitätsurteile möglicherweise gemeinsam von den gleichen Nervenzellen verarbeitet werden“, so Giese. „Beide Funktionen greifen scheinbar auf überlappende Gehirnbereiche zurück.“ Die Forscher vermuten, dass höhere Formen der Kausalitätswahrnehmung aus einfachen Mechanismen der Bewegungserkennung und Interpretation entstanden sein könnten.

Originalpublikation:
Vittorio Caggiano, Falk Fleischer, Jörn K. Pomper, Martin Giese & Peter Thier (2016): Mirror neurons in monkey premotor area F5 show tuning for critical features of visual causality perception. dx.doi.org/10.1016/j.cub.2016.10.007

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Computational Sensomotorics

Contact: Prof. Dr. Martin A. Giese

Dr. Nikić is currently setting up her laboratory. The CIN’s very own microscope capable of “super” resolutions of ca. 20 nanometers, a N-STORM by Nikon, has just been delivered. But in other areas, the research group leader has not yet finished the setting-up process of acquiring important equipment, as well as hiring lab personnel. With the grant (1.3 million Euros over five years) by the Emmy Noether Programme, she will be able to purchase additional equipment and hire staff.

Nikić is going to investigate into axonal damage in neuroinflammatory diseases. Axons are long extensions of neurons, used to communicate with other neurons and to connect to other brain areas. Axons are very vulnerable to infiltrating immune cells in case of inflammatory disease, such as MS in the central nervous system, often massively impairing brain functions. Ivana Nikić will concentrate on a form of neuroinflammatory axon damage called Focal Axonal Degeneration (FAD), that she discovered herself. To a certain extent early stages of FAD are reversible, so investigating its mechanisms on the molecular level might lead to clues how this and other forms of neuroinflammatory axon damage can be treated.

More in-depth research on imperfectly understood neuroinflammatory diseases such as MS is of the utmost importance. Therefore, it is good news that a young biologist active in this field was chosen by the DFG for their prestigious programme. Given the strict criteria for application, not to mention the rate of rejected proposals (ca. 80% according to the DFG itself), the grant constitutes a major success.

Still, Ivana Nikić herself remains grounded enough: “Of course I am overjoyed, this is a great honour, and a great opportunity! Personally, I just want to set up my research group. The Emmy Noether Programme will give me a lot of financial leeway in this, which I am extremely grateful for. Now it is time to get to work.”

Dr. Ivana Nikić, born 1981 in Belgrade, studied Molecular Biology and Physiology in Belgrade. She received her PhD in Human Biology at the Medical Faculty of Ludwig-Maximilian University, Munich, in 2011, for her work on axon damage in the context of multiple sclerosis. For this work, she also received the “Dr. Hildegard und Heinrich Fuchs Preis zur Förderung des medizinischen Nachwuchses”, an award for the best thesis of the Medical Faculty (LMU, Munich), in 2012. From 2012 to 2016, she was a postdoctoral fellow at EMBL, Heidelberg, with an EMBO Long-Term Fellowship and a Marie Curie IntraEuropean Fellowship.

Emmy Noether (1882–1935) was a renowned mathematician of the 20th century. Although the theorem named after her is part of the basis for mathematical physics and she was one of the first female German mathematicians to qualify as a professor, she never received a full professorship in Germany. Since 1997, the DFG’s Emmy Noether Programme provides outstanding scientists and early career researchers an alternative path to professorship. It is intended to provide early career researchers with the opportunity to rapidly qualify for a leading position in science and research or for a university teaching career by leading an independent junior research group and assuming relevant teaching duties, without the need for a habilitation. As of 2015, the programme included 329 projects.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

While recording brain activity using magnetoencephalography (MEG) to monitor activity in motor areas, Pape and Siegel set 20 human subjects the simple task of deciding whether or not a field of dots on a screen was slowly moving together. The subjects could respond “yes” or “no” by pressing a button with either their left or their right hand. The mapping from choice (yes/no) to response (left/right button) changed randomly on each trial, with a short cue telling subjects the current configuration. This ensured the participants’ brains could not plan a motor response, i.e. the correct button press, during choice formation. Astonishingly, while the test subjects were able to press the ‘correct’ button most of the time, subjects still showed a strong tendency towards motor response alternation. In other words, they often simply pressed the button they had not pressed in the trial just prior to the current one. This tendency was pronounced enough to detract from subjects’ overall decision task performance.

In their MEG data, Pape and Siegel found a neural correlate of this tendency in the motor cortex itself. They showed that the upcoming motor decision can be predicted from the status of motor areas even before decision formation has begun. This pre-decisional motor activity to a large extent originates from the neural residue of the previous motor response. How often the subjects alternated between response alternatives is predicted by how pronounced the previous response’s vestiges in the motor cortex still are. Together, these results suggest that the status of the motor cortex even before decision making can influence the formation of a given choice.

These results challenge the traditional view of decision making. According to this view, decisions are formed in the prefrontal cortex and fronto-parietal cortex, brain regions that are associated with ‘higher’ brain functions that are essential for memory and problem solving. The motor cortex is seen as the structure merely executing the behaviour that those ‘higher’ brain regions have determined. Contrary to this view, Pape and Siegel’s findings suggest that the motor cortex also plays a role in informing decision-based behaviour.

Does that mean the way we respond to our environment is not a matter of choice after all? Do we just randomly ‘decide’ what to do based on the state our motor cortex happens to be in? Anna-Antonia Pape, who recorded and analysed the data, does not think so: “The effect is there, yes, but I wouldn’t link it to the question of free will by any means! Higher brain areas are still very important for the decision making process, but now we know that motor areas can tip the scales.”

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

Wenn jeder der tausenden von Duftstoffen, denen wir im Alltag begegnen, eine direkte Repräsentation im Gehirn hätte, dann könnte man einzelne Gerüche auch in komplizierten, zuvor noch nicht wahrgenommenen Geruchsmixturen erkennen. Tatsächlich aber wird es umso schwieriger, einen Geruchsstoff zu identifizieren, je mehr Gerüche gleichzeitig vorhanden sind – ganz ähnlich, wie es Probleme bereitet, auf einer lauten Party einem Gespräch zu folgen. Der Riechkolben, in dem die Riechwahrnehmung im Gehirn beginnt, kann eine solche Aufgabe nicht perfekt erfüllen. Daraus folgt, dass die zur Verfügung stehenden Rezeptoren zur Geruchserkennung nicht auf einer Eins-zu-eins-Basis verwendet werden. Stattdessen sind die Glomeruli – das sind die Strukturen in der Oberfläche des Riechkolbens, wo die Informationen aus der Nase zuerst ankommen – an der Erkennung einer Vielzahl von Gerüchen beteiligt.

Dass wir trotzdem viele einzelne Duftkomponenten erkennen können, dafür sorgt ein noch unbekannter Mechanismus. Um ihn aufzuklären, haben die Neurowissenschaftler um Professor Matthias Bethge vom Tübinger CIN und Professor Venkatesh Murthy von der Harvard University Daten analysiert, die aus einer Reihe von Verhaltensexperimenten mit Mäusen stammen. In diesen Experimenten sollten die Mäuse jeweils die Existenz eines von zwei Gerüchen in einem Gemisch mit bis zu 14 weiteren Duftstoffen feststellen. Bei theoretisch über 50.000 möglichen Gemischen konnten die Nager nach ca. 1.000 Trainingsdurchläufen in mehr als 90 Prozent der Experimente einen der beiden erlernten Düfte richtig identifizieren. War der erlernte Duft nur mit wenigen anderen Komponenten vermischt und wiederholten sich die Mixturen nicht, dann lag die Quote bei fast  100 Prozent. Erst bei komplexen Geruchsmixturen oder wenn Teile der Zusammensetzung wiederholt und nur leicht variiert wurden, versagten die Mäuse etwas häufiger.

Diese Treffsicherheit in der Erkennung von Geruchskomponenten versuchten die Forscher nun, einfachen lernfähigen Computerprogrammen „beizubringen“, mit denen sie ebenfalls tausende von Experimentreihen durchspielten. Durch die Gegenüberstellung der Leistungen verschiedener Algorithmen mit den Leistungen der Mäuse gelang ihnen der Nachweis, dass ein einfaches lineares Verfahren basierend auf den Glomeruli ähnlich leistungsfähig ist wie das Mäusegehirn. Damit dieser Algorithmus funktioniert, muss er ähnlich wie die Mäuse trainiert werden. Wie anschließend die Aktivitäten der Glomeruli ausgelesen werden, hängt stark von der Art des Trainings ab. Wenn der Algorithmus nur mit einzelnen Gerüchen trainiert wird, macht er deutlich mehr Fehler bei der Geruchserkennung in Mischungen, was an der unspezifischen Kodierung in den Glomeruli liegt.

Würde das Lernen im Gehirn aber nicht auf Glomeruli, sondern vielmehr auf einer Repräsentation der einzelnen Geruchskomponenten im Gehirn beruhen, so sollte die Verallgemeinerung des Lernens von einzelnen Gerüchen auf Mischungen einfach sein. Diese Vorhersage wurde dann auch bei Mäusen getestet. Tatsächlich hatten die Mäuse Schwierigkeiten, einzelne Gerüche unter mehr als vier anderen zu erkennen, so wie es durch das Verhalten des Algorithmus vorhergesagt wurde. Daher ist es wahrscheinlich, dass das Gehirn eine Geruchsmixtur – anders als bisweilen angenommen – wohl nicht in ihre Geruchskomponenten zerlegt. Beim Sehen sind wir es gewohnt, dass wir Objekte auch dann in Bildern mühelos erkennen können, wenn wir das Objekt nur einmal vorher gesehen haben. Bei Geruchsmixturen dagegen müssen wir uns vor allem auf den Gesamteindruck verlassen, während die Zerlegung in Einzelgerüche erst mit viel Erfahrung gelernt werden kann.

Publikation:
Alexander Mathis, Dan Rokni, Vikrant Kapoor, Matthias Bethge, Venkatesh N. Murthy: Reading Out Olfactory Receptors: Feedforward Circuits Detect Odors in Mixtures without Demixing. Neuron 91 2016. 10.7554/eLife.16290.
dx.doi.org/10.1016/j.neuron.2016.08.007

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Computational Neuroscience

Contact: Prof. Dr. Matthias Bethge

“It was extremely exciting to actually see these cells and their connections under the microscope for the first time”, says Dr. Burgalossi. “They had been a scientific ghost for such a long time.” The cells whose discovery so elates the Tübingen neuroscientist are called HD cells. Their existence was stipulated in the early 1990s, including their function: HD cells recognise the head’s current angle and facing, a simple yet essential part of recognising one’s place in space, and thus of navigation.

But until now, HD cells and their connections with other brain areas had not been identified and observed. The Tübingen researchers were the first to successfully identify them in rats’ brains and observe them microscopically. The researchers found their target by inserting hair-thin glass electrodes into the presubiculum, a brain area that had been previously shown to contain HD cells. These electrodes detected the small electrical impulses in the cell they were attached to, generated whenever the rat was facing a particular direction. The presubiculum consists of several layers, which contain different types of neurons. Not all of them are HD cells. “HD cells have a specific morphology and are predominantly found in layer 3 of the presubiculum. We found no HD cells in layer 2, where the neurons also look different”, Burgalossi explains, “now we have proven that there is a strong relationship between structure and function.” This structure-function relationship can be considered the holy grail of neuroscience, as it allows researchers to not only say ‘this part of the brain does that’, but also lets them gain insights into how the individual neurons do their job.

Moreover, the researchers’ work provides the first piece of evidence that could explain how HD cells forward information from the presubiculum to other brain areas concerned with navigation. In the brain, networks are formed by axons, long and extremely thin appendages that allow neurons to connect to each other. Axons are the ‘wiring’ that makes up the brain’s ‘circuitry’. They can grow to several millimeters in length even in the tiny brains of rodents, while being only about one micrometer in diameter. These dimensions are also the reason why it is so hard to collect direct evidence of network connections between brain structures. Identifying individual neurons under the microscope is done by injecting dyes into the cell body. But neurons are so thin and their axons can be so long that this is no guarantee one actually gets to see one: “The difficult part of our job is often the labeling procedures” says Burgalossi. “Only if you can efficiently fill a HD cell with dye will you be able to find out which specific neuron – among the many different types in the brain – you have before you, and discover where it projects”.

The team found that HD cells in the presubiculum feed information into the medial entorhinal cortex (MEC), a brain area attracting much attention in neuroscience: this is where the fabled ‘grid cells’ are located, a recently discovered type of neuron that got its name from the way its activity forms a very regular ‘grid-map’ of the environment. The discovery of grid cells earned the Norwegian scientist couple Edvard and May-Britt Moser the Nobel Prize in Physiology or Medicine in 2014. The Tübingen neuroscientists’ new results provide the first anatomical evidence of how the entorhinal grid cell area might be functionally connected to the rest of the brain’s navigational apparatus, in particular with HD cells. Neuroscience is one step closer to understanding the inner compass now.

Publication:
Patricia Preston-Ferrer, Stefano Coletta, Markus Frey, Andrea Burgalossi: Anatomical Organization of Presubicular Head-Direction Circuits. eLife. 10 June 2016. pii: e14592.

Read the full article here.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neural Circuits and Behavior

Contact: Dr. Andrea Burgalossi

Seeing – arguably our most important way of perceiving the world – mostly happens without conscious intent. We see much better in the center of our visual field (along the visual axis) than in the periphery. So when our brain detects an object of interest in the periphery of our visual field, it immediately initiates an eye movement so our visual axis intersects with those objects. Once an object is in our direct line of sight, we can perceive it in far more depth and detail.

This is partly due to the much greater density of photoreceptor cells in a very small area in the center of the retina – the fovea. But the preference of visual perception for the center of our visual field is also represented in the brain: it is mirrored in those brain structures that process stimuli transmitted from the fovea. For instance, within the superior colliculus (SC) – a midbrain area that initiates eye movements to peripheral stimuli directly based on input from the eyes –, much more neural tissue is dedicated to processing foveal signals than to processing peripheral signals. This phenomenon is called foveal magnification.

Now Dr. Hafed’s team has shown that besides the fovea, other parts of the visual field are also ‚magnified’ in the SC. Their findings reveal that the currently accepted model of the SC, which only accounts for foveal magnification, is not sufficient. This simple model in effect assumes that our SC looks at the world through a magnifying lens: The closer to the center of our visual field an object is, the more distinctively it is picked up by specific neurons, and the more such neurons are dedicated to processing it.

Dr. Hafed's new model modifies this image, adding upper visual field magnification on top of foveal magnification. His team has found that the upper half of the visual field is represented in the SC by receptive fields that are much smaller, more finely tuned to the spatial structure of received images, and more sensitive to image contrast. On the other hand, the lower visual field is represented at a lower resolution. Thus, Hafed's team thinks of the ‚lens’ in the SC more as bifocal glasses.

To Dr. Hafed, the asymmetry in neural representation is adapted to our everyday environment. Far objects project smaller images on our retina than near objects. Therefore, processing images of near objects in a way that lets us react quickly and usefully to them needs less resolution than objects that are far away. 'In our three-dimensional environments, objects in the lower half of our visual field are usually close, a part of near space. An example would be the instruments in a car as we drive, which are low and close to us', Hafed explains. 'Meanwhile, objects in far space, such as an upcoming intersection, are viewed in the upper half of our visual field. In order to be able to focus precisely on objects that are far away, we intuitively need higher resolution in the upper visual field. Our experiments provide substantial evidence that the old model, with its symmetrical representation of upper and lower visual fields in the SC, needs to be rethought.'

The findings of Hafed’s team may greatly benefit user-interface design in augmented reality (AR) or virtual reality (VR) systems. Their insight that the SC ‚bifocals’ directly translate into faster and more accurate eye movements towards the upper visual field could help in strategic placement of essential feedback requiring rapid orienting. AR and VR systems feature large, immersive displays covering almost the entire visual field. In such scenarios, computer systems have tremendous freedom in the placement of essential user feedback, and optimizing such placement according to the ‚human factor’ currently represents a significant challenge for engineering.

Publication:
Ziad M. Hafed, Chih-Yang Chen: Sharper, Stronger, Faster Upper Visual Field Representation in Primate Superior Colliculus. Current Biology (in press).

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Physiology of Active Vision

Contact: Prof. Dr. Ziad Hafed

Good science is supposed to be "frugal", i.e., it ought to make use of as few assumptions and abstractions as possible. In neuroscience, the abstract concept of "attention" is a concept that is considerably less frugal than would be desirable. It is basically a black box and does not necessarily explain which processes in the brain it actually addresses – a central question of perception research today.

For several decades, "attention" was thought to be a barely definable state of certain brain regions. In visual perception, for instance, eye movements towards a stimulus are triggered in the Superior Colliculus, a part of the midbrain. The direction of attention in the brain does not react equally to all stimuli, though: when there is a high level of "attention in the sensory system, reactions are swift and intense; neuroscientists call this state "attentional capture". A state of slow and comparatively weak reactions, on the other hand, is called "inhibition of return" (IOR). Attentional capture and IOR both follow an alternating pattern, which rides on a rhythm with approximately 10 oscillations per second.

But what causes this rhythm, and how does "attention" control it? The international research team have now been able to depict the processes which might be responsible in a surprisingly simple model. These CIN and NIPS  neuroscientists have been cooperating for several years now, headed by Dr. Ziad Hafed (Tübingen). They are investigating a phenomenon whose importance for visual perception has long been underestimated: tiny eye movements, so-called microsaccades. These small adjustments constantly correct the axis of vision when the gaze fixates an object. In earlier studies, Hafed and colleagues had found that microsaccades are generated in the Superior Colliculus in a stable rhythm that is reset by new stimuli entering the visual field. Microsaccades also change direction with each iteration.

Following up on these observations, Hafed and his team arrived at a hypothesis: what if the rhythm and direction of microsaccades directly trigger attentional capture and IOR? They developed a theoretical and computer model based on this assumption, employing a wide range of parameters to see what predictions the model could make. Testing the model's predictions in experiments, the researchers surprised even themselves: they found that besides microsaccades, no additional factors were necessary in the model to explain attentional capture and IOR.

Ziad Hafed states that "attention" may be explained quite "parsimoniously". He believes that the brain filters "important" stimuli simply based on saccadic corrections of the direction of gaze. These eye movements directly produce the phenomena which have so far been described as attentional capture and IOR. Which of these two occurs depends on the timing and direction of the stimulus relative to the microsaccadic rhythm and direction. 'These findings are a strong argument that the mechanism of "attention" is based on a very simple principle', says Hafed. 'Should they be validated by further studies, results from decades of research would have to be seen in a very different light.'

Publications:
1. Ziad M. Hafed, Chih-Yang Chen, Xiaogang Tian: Vision, Perception, and Attention through the Lens of Microsaccades: Mechanisms and Implications. Frontiers in Systems Neuroscience. 2. Dezember 2015. (doi: 10.3389/fnsys.2015.00167).
2. Xiaoguang Tian, Masatoshi Yoshida, Ziad M. Hafed: A Microsaccadic Account of Attentional Capture and Inhibition of Return in Posner Cueing. Frontiers in Systems Neuroscience (im Druck). 22. Februar 2016.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Physiology of Active Vision

Contact: Prof. Dr. Ziad Hafed

Memory is one of the most important functions of our brain. Not only does it allow us to regale our grandchildren with the exploits of our youth; it is essential for many everyday procedures. Our memory is constantly and immediately active whenever we experience a new thing. For instance, after meeting somebody only once, we still recognise them after hours or days. And even when we go somewhere for the first time - for instance, the perfume section of a department store, a particular office in a building, or the toilet in a restaurant - we will usually be able to find our way to the exit without a problem.

So our memory is not only constantly alert, it also constructs new recollections very quickly – often during the first interaction. The reason for this alacrity of memory formation is the fact that for every person, every place – and probably a lot of other concepts, too – there are individual memory cells that are specifically assigned to that memory. One subtype of these neurons called granule cells is situated in the hippocampus, a centrally located brain area. Whenever memory concepts like “my living room” or “Angela Merkel” are activated – e.g. by stepping into the living room or by seeing a photo of the German chancellor – the small number of granule cells associated with that memory become activated in the form of electrical discharges. The large majority of the remaining neurons, however, remain dormant.

Up to now, the mechanisms through which individual granule cells are assigned to specific memories were not understood. The question of whether ‘silent’ granule cells can become activated under certain circumstances proved particularly intriguing. The Tübingen research team led by Dr. Andrea Burgalossi worked on the assumption that granule cells which receive electrical impulses can be ‘un-silenced’ and thus become memory cells. To confirm their hypothesis, they inserted hair-thin microelectrodes into the dentate gyrus of rats – an area within the hippocampus which is responsible for memories of space and location – allowing them to send weak electrical impulses to individual granule cells.

The rats were allowed to explore a simple labyrinth, and at a specific location within this labyrinth, individual granule cells were stimulated with weak electrical pulses (in the nanoampere range) via the microelectrode. The same electrode allowed the researchers to measure the subsequent activity of the stimulated cells. The result: whenever the rats arrived at the same spot within the labyrinth where the original impulse had been administered, stimulated granule cells now fired spontaneously. The electrical impulse had thus induced the individual granule cells to form a place memory.

Moreover, Dr. Burgalossi and his team found that the duration and temporal pattern of the impulses administered play a large role. The impulses formed more durable place memories when they followed the natural theta-rhythm of the brain – a periodic increase and decrease in electrical potential which takes place roughly 4 to 12 times per second. Another finding could turn out to be of equal importance: rats that were new to the labyrinth reacted much more keenly to the induced place memory than rats that had been given the run of the labyrinth beforehand. Apparently, memory cells can be activated more easily when the brain is exposed to novel information.

These new insights into memory formation shed light on one of the most important functions of the human brain. And though there is still much to do before fundamental findings like these can offer new strategies for the treatment of brain diseases which affect memory formation (e.g. Alzheimer’s disease, Parkinson, dementia), they represent an indispensable first step on the way.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neural Circuits and Behavior

Contact: Dr. Andrea Burgalossi

“What the frog’s eye tells the frog’s brain” was the title that cognition scientist Jerome Lettvin gave to a seminal paper published in 1959. He assumed that the eye not only sees, but also processes images – even before they are transmitted to the brain for further processing. Lettvin was able to show that the eye neither simply takes pictures like a camera, nor does it send them to the brain without filtering. Instead, the eye itself extracts valuable information from what it sees. In the case of the frog, for example, it might ‘tell’ the brain: “There is something small and dark there, possibly a fly.” For his revolutionary hypotheses, Lettvin was at first laughed off stage at conferences. In the meantime, though, his oft-quoted paper is considered a milestone. The questions raised in Lettvin’s time are still pursued by scientists today.

A Tübingen-based team of researchers has now tackled these questions anew, led by Prof. Thomas Euler and Prof. Matthias Bethge (Werner Reichardt Centre for Integrative Neuroscience, Bernstein Center for Computational Neuroscience, and Institute for Ophthalmic Research). The neuroscientists wanted to find out which kinds of information about the world the retina transmits to the brain. To this end, they undertook a study on an unheard-of scale, investigating more than 11,000 individual retinal cells in mice - far bigger than the largest similar study to date, which had been content with investigating approx. 450 individual cells.

Combining state-of-the-art experimental methods, the researchers studied retinal ganglion cells (RGCs). They made use of electroporation, a staining technique which makes whole populations of nerve cells visible under the microscope. This enabled the researchers to watch individual cells at work in real time. The vast amounts of data were analyzed using advanced machine learning techniques. The scientists were most interested in the diverse functions of these cells: different ganglion cells respond to different properties of images, and send this information to the brain via different channels, each specialized in either contrast, color, direction and movement, edges etc. From these information channels, the brain assembles our image of the world surrounding us. The scientists tested for the response behavior of the ganglion cells to various simple images and moving optical stimuli.

Based on this functional differentiation, the team was able to identify up to 40 types of ganglion cells in the retina, very likely representing as many information channels. This is far more than the at most 20 types which had been heretofore assumed. While the results from the mouse model cannot be applied directly to humans, the retina is similar in all mammals. This brings an analogous classification in humans within reach.

The large number of different information channels suggests that the retina does not simply transform received light signals into nerve cell signals. Instead, it also interprets the signals in fundamental ways. Their work in basic research has brought the Tübingen neuroscientists a large step closer to understanding how images are interpreted in the brain. Since many diseases of the eye only affect certain retinal cell types and channels, these insights can also help in developing more specific treatments. In Tübingen, research on prosthetic technology to restore sight to blind people (retina implants) has been going strong for many years. This research stands to profit massively from the new results: current models still stimulate the retina relatively unspecifically. New insights provided by the study at hand might help future versions to feed visual information directly into suitable channels.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

Das Forscherteam unter Beteiligung von Dr. Philipp Berens und Professor Matthias Bethge vom CIN, Professor Rickard Sandberg vom Karolinska Institutet in Stockholm und Dr. Andreas Tolias vom Baylor College of Medicine in Houston/Texas wählte für seine Untersuchungen den Neo-cortex bei Säugetieren, der für höhere Hirnfunktionen zuständig ist. Dies sind beim Menschen beispielsweise das räumliche Vorstellungsvermögen, bewusstes Denken und Sprache. In der sehr dünnen äußersten Schicht des Neocortex gibt es nur zwei Typen von Nervenzellen. Die Wissenschaftler können sie anhand ihrer Gestalt (Morphologie) als auch anhand ihrer Aktivitätsmuster (Physiologie) unterscheiden.

Prinzipiell sind bei Unterschieden in der Morphologie und Physiologie auch unterschiedliche Muster der Genaktivität zu erwarten. Aktive Gene werden in der Zelle in eine entsprechende Ribonukleinsäure (RNA) kopiert, die die Wissenschaftler mit Hilfe der von ihnen entwickelten neuen Methode nun sogar in einzelnen Zellen im intakten Gewebe messen können. In der Studie gingen sie der Frage nach, ob sie dieses genetische Profil einzelner Nervenzellen direkt mit ihrer Physiologie und Morphologie in Verbindung bringen können. Sie nahmen an Mäusen elektrophysiologische Messungen an einzelnen lebenden Zellen vor, während sie gleichzeitig RNA-Moleküle daraus absaugten. In einem Prozess, den die Forscher „Patch-seq“ nennen, verbanden die Forscher zwei Methoden miteinander: „Patching“ bezeichnet eine bestimmte Art und Weise, die elektrischen Impulse an einer Nervenzelle zu messen; Sequenzierung ist das Auslesen eines Gens oder wie hier der RNA. So gelang ihnen erstmals eine eindeutige Zuordnung genetisch bestimmter Zelltypen zu den gleichzeitig gemessenen physiologischen Eigenschaften. Die von den Tübinger Wissenschaftlern beigesteuerten Lernalgorithmen waren darüber hinaus in der Lage, die Morphologie und Physiologie der betreffenden Zellen vorherzusagen.

Ein vielversprechendes Ergebnis der Studie: Einer der beiden untersuchten Zelltypen zeigt eine besonders hohe Aktivität bei vier Genen, die im Verdacht stehen, für autistische Störungen und bestimmte Formen der Schizophrenie verantwortlich zu sein. Die Wissenschaftler erhoffen sich daraus ein besseres Verständnis der Wirkmechanismen dieser Krankheiten. Auch sonst steht den Neurowissenschaften nun ein Instrument zur Verfügung, mit dessen Hilfe eine Synthese genetischer und physiologischer Erklärungsansätze möglich ist.Pressemitteilung nur auf Deutsch verfügbar.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Computational Neuroscience

Contact: Prof. Dr. Philipp Berens

We grow older than ever before in human history: people born today can expect a lifespan greater than a century. But where the individual sees promises of a long life, our society faces a fundamental transition – and we are only beginning to perceive its effects. Moreover, old age is associated with deep-seated worries and fears. So it comes as no surprise that the public discourse is a discourse of crisis, with all the horror scenarios and cliché that this entails.

But is it desirable for the individual, and is it useful for our society, to see ageing solely as a process of degeneration – as physical and mental decline? Science, art and philosophy are starting to make an increasingly convincing case that we need a more differentiated view than the stereotype “old age equals degeneration”.

In old age, we develop some abilities that we did not have in earlier parts of our lives, and expand upon others, for instance emotional intelligence, certain forms of linguistic competence etc. This process can be adequately described not as a mere degeneration, but as a transformation. The brain reorganises and reorders itself, allowing us to draw on formerly unavailable capabilities. This specific potential in the ever-increasing number of elderly people society as a whole could put to constructive use.

This year’s CIN Dialogue undertakes to contribute to a differentiated discourse on age(ing) and its consequences. The discussants are: leading Alzheimer’s researcher Konrad Beyreuther, psychologist and cognitive scientist Jochen Brandtstädter and philosopher Thomas Rentsch. Wieland Backes will chair the discussion.

Location: Lecture Hall Audimax, Neue Aula, University of Tübingen

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Wissenschaftler lieben Modelle. Sie träumen davon, die Wirklichkeit so exakt wie möglich nachzubilden – und zugleich so einfach wie möglich. Aber je komplexer der untersuchte Gegenstand, desto mehr muss man das Modell vereinfachen. Das Gehirn, diese vielleicht komplexeste Struktur des Universums, scheint sich der Modellbildung daher zu entziehen. Doch die Technik stößt mittlerweile in Bereiche vor, die die Nachbildung von Hirnfunktionen im Computer in greifbare Nähe rückt. Inzwischen befasst sich ein ganzer Bereich der Hirnforschung, die „Computational Neu-oscience“ („berechnungsgestützte Neurowissenschaft“) damit, neuronale Netzwerke und ihren Aufbau zu verstehen und Computermodelle zur Nachbildung bestimmter Hirnfunktionen zu schaffen.

Diese Möglichkeiten machte sich nun eine Kooperation zwischen zwei Tübinger Vertretern dieser Zunft, Dr. Alexander Ecker und Bernsteinpreisträger Dr. Philipp Berens (beide Werner Reichardt Centrum für Integrative Neurowissenschaften – CIN an der Universität Tübingen), und einem Forscherteam um Dr. Andreas Tolias (Baylor College of Medicine, Hous-ton/Texas) zunutze. Während in Texas mit Hilfe fortgeschrittener Mikroskopier- und Schneidetechniken einzelne Nervenzellen aus dem Neocortex – einem Teil der Hirnrinde, der die höheren Hirnfunktionen beheimatet – von Mäusen isoliert wurden, analysierten die Tübinger Forscher die Daten.

Insgesamt wurden 2200 einzelne Zellen untersucht. Die Neurowissenschaftler sprechen von „Popu-lationen“, die sie mit einem „Zensus“ erfassen – eine „Volkszählung“ im Gehirn sozusagen. Eine derart umfassende Untersuchung individueller Zellen war bisher nicht versucht worden. Bis vor Kurzem fehlten dazu sowohl die technischen Möglichkeiten als auch die der Analyse. Da bereits eine einzelne Nervenzelle ein hochkomplexes Gebilde ist, ist die Kategorisierung gleich einiger Tausend davon extrem aufwändig. Doch dem Forscherteam gelang es, Algorithmen zu entwickeln, die Zellen anhand ihrer Morphologie – ihrer Form und Beschaffenheit – 15 verschiedenen Typen zuordnen können: eine für die Forscher überraschend große Zahl.

Die untersuchten Interneurone sind Nervenzellen, die keine Verbindungen zu anderen Hirnarealen herstellen, sondern sich mit ihrer „Nachbarschaft“ zu komplexen Schaltkreisen vernetzen, die bisher wenig untersucht sind. Die Forscher vollzogen nun erstmals genau nach, welche der 15 Arten von Interneuronen mit welchen ihrer Nachbarn verbunden sind – „Konnektivität“ nennen sie die Verbin-dungseigenschaften von Nervenzellen. Die Forscher fanden Hinweise, dass die 15 Zelltypen sich drei Kategorien zuordnen lassen: Interneuronen, die nur mit ihresgleichen verbunden sind, Interneu-ronen, die nur einen anderen Zelltyp ansteuern (die sogenannten Pyramidalzellen), und solche, die mit allen Arten von Nachbarzellen Verbindungen eingehen.

Die Daten zur Konnektivität der Interneuronen können nun zur Erstellung von Computermodellen dienen. Wie immer streben die Forscher nach einem Modell, das die komplizierte Wirklichkeit möglichst vereinfacht, dabei aber noch aussagekräftig ist. Die Reduktion der 15 Typen auf drei Kategorien ist ein solcher Fall eines vereinfachten, aber aussagekräftigen Modells. Das ermöglicht weitgehende Schlüsse, so Philipp Berens: „Zum einen erlaubt uns so eine Arbeit, überhaupt zu verstehen, wie die Morphologie und die Konnektivität eines Zelltyps seine Funktion bestimmt. Zum anderen kann man sich fragen, ob diese Zelltypvielfalt für komplexe Berechnungen notwendig ist, oder ob es auch einfacher geht, bzw. wofür diese Vielfalt gut ist.“

Dazu gibt die nächste „Volkszählung“ vielleicht noch weitere Hinweise: „Vergleichende Studien zu anderen Hirnarealen und Spezies wären sehr interessant“, meint Alexander Ecker. „In Texas haben sie damit schon begonnen.“

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Computational Neuroscience

Contact: Prof. Dr. Philipp Berens

Beauty is not the only thing that lies in the eye of the beholder – everything that we see is first analysed in the eye itself. Before the retina relays visual information to the brain, more than 80 types of neurons compute image properties such as contrast, brightness, and colour. More complex aspects such as edges and movements are likewise first detected in the eye. Much like a biological switchboard, retinal neurons form diverse circuits in multiple layers, giving the newly established project its name. The research network aims at understanding structure and functional organisa-tion of these neuronal circuits in the retina. To do so, it will offer fifteen 3-year PhD student positions, financed with the funds provided by the EU.

‘switchBoard’ prevailed in a highly competitive field to reach this point – in 2015, only 106 of more than 1,300 applicant projects in the framework of the Marie Skłodowska-Curie Actions (MSCA) programme were successful in obtaining funding from the European Commission. The MSCA programme is part of the EU’s Horizon 2020 Research and Innovation Framework Programme. It was established to generate a larger pool of researchers in Europe and thus strengthen its scientific standing world-wide. Among other projects, the programme funds networks specialising in the structured training of junior researchers, in this case a so-called ‘Innovative Training Network’ (ITN). Besides individual scientific training, ITNs include a number of overarching measures such as summer schools, scientific training seminars, soft skill courses and workshops, which are mandatory for all 15 ‘switchBoard’ PhD students. Furthermore, ITNs promote mobility within the EU: to receive training, all junior researchers must relocate to a country different from the one where they received undergraduate training and/or worked in the past 3 years.

The project will be coordinated by Prof. Dr. Thomas Euler of the Werner Reichardt Centre for Inte-grative Neuroscience (CIN) at Tübingen University and the Institute for Ophthalmic Research. Prof. Euler is very pleased with how the project commenced, commenting: ‘This kind of international and interdisciplinary research network is a great opportunity for young researchers to get to know a range of possibilities in neuroscience. It enables them to make important career decisions. Also, a network such as ‘switchBoard’ allows us to tackle more complex questions, for instance: how does the retina deal with this incredible stream of data flooding into the eye such that important information is filtered out and encoded for the brain.’

Find more information at / mehr Informationen unter: www.etn-switchBoard.eu.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

How we feel what we feel: this question has kept neuroscience busy for a long time. The problem is fundamentally interesting, in that we know less about the sense of touch than any other of our five senses – even though the corresponding sensory organ, the skin, covers our entire bodies. But more importantly, millions of pain patients all over the world could expect more efficacious help if we knew more about the origins of our tactile sense.

Pushing, pulling, piercing, chafing – these words can describe perceptions of touch, but in exaggerated form, they can also become sources of pain. A mechanical contact produces an electrical impulse in the cellular membranes of neurons that conduct touch stimuli to the brain, the so-called mechanoreceptors. How this happens, and which biochemical and biophysical mechanisms are at work, though, nobody was able to answer until relatively recently. Since the 1980s we have at least known that ion channels play a major role: when the nerve cell is deformed, this stimulates certain proteins that run right through the cell membrane like a channel. The deformation opens this protein channel for a specific kind of ion, which enters the cell and produces an electrical impulse.

Dr. Hu and her team were now able to show that this is not all: the cell membrane surrounding the ion channels is just as important. If it is soft, it easily yields to pressure, which does not create an impulse. But if it is more rigid, the ion channels in the area respond strongly to the deformation.

The behaviour of these cell membranes is controlled by two substances. That molecule of ill repute, cholesterol, has been well-known for a long time. But Hu and her colleagues now showed that – at least in mice – „stomatin-like protein‑3“, or STOML3, plays a decisive role too. Only the interaction of cholesterol and STOML3 effects a stiffening of the cell membrane under soft pressure. This makes the activation of surrounding ion channels possible. If one of the pieces of this puzzle is not present, or if their reaction is disrupted, there is no stimulus.

Through behavioural studies in mice, the scientists showed that this mechanism could apply similarly in human pain patients. If new drugs are developed following this line of inquiry, even patients suffering from allodynia might stand to benefit in the future: this condition turns even the slightest of touches into intense pain.

Publication:

Yanmei Qi, Laura Andolfi, Flavia Frattini, Florian Mayer, Marco Lazzarino & Jing Hu: Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons. Nature Communications 6: 8512, October 7th, 2015.

http://www.nature.com/ncomms/2015/151007/ncomms9512/full/ncomms9512.html

http://dx.doi.org/10.1038/ncomms9512

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Sensory Mechanotransduction: Ion Channels and Mechanism

Contact: Dr. Jing Hu

In unserer Netzhaut existieren viele verschiedene Typen einer bestimmten Zellart, der Bipolarzellen. Mittlerweile sind 14 Unterarten bei der Maus bekannt. Wie kommt diese Vielfalt zustande – und erfüllen die Zellen unterschiedliche Rollen bei der visuellen Verarbeitung? Mit diesen Fragen beschäftigt sich Philipp Berens. „Mithilfe von Computermodellen versuche ich, die funktionalen und biophysikalischen Eigenschaften dieser Zellen zu verstehen“, erklärt Berens. „Meine Modelle bauen dabei auf physiologischen und anatomischen Daten aus experimenteller Forschung auf.“ Die Computermodellierung ermöglicht ihm, den Wissensstand über die Nervenzellen zu testen: Liefern die Modelle andere Ergebnisse als die Messungen an lebenden Zellen, dann herrscht noch eine Wissenslücke vor, die geschlossen werden muss.

In den letzten Jahren hat Berens mit seinen experimentell arbeitenden Kooperationspartnern bereits Ganglienzellen untersucht, eine weitere Zellklasse der Netzhaut. Diese erhalten ihre Eingangssignale von den Bipolarzellen und sind ihnen damit auf dem Weg vom Licht zum Nervenimpuls im Gehirn nachgeschaltet. Mit statistischer Datenanalyse hat er verschiedene Typen von Ganglienzellen klassifiziert. „Dabei hat sich herausgestellt, dass es nicht – wie bis dahin angenommen – eine Handvoll Ganglienzellarten gibt, sondern 30 bis 40 unterschiedliche Typen. Sie alle erfüllen eine unterschiedliche Funktion und schicken eine eigene Bildversion an das Gehirn“, so Berens.

Die Erforschung der Bipolarzellen ermöglicht dem Hirnforscher, die große Vielfalt der Ganglienzellen zu verstehen. Gleichzeitig verfolgt Berens mit seiner Arbeit medizinische Anwendungsmöglichkeiten: So wird er in einem weiteren Schritt untersuchen, welche Auswirkungen degenerative Netzhauterkrankungen auf verschiedene Zelltypen haben. „Fallen alle Bipolarzellen gleichzeitig aus oder überleben manche Typen länger als andere? Und ergibt sich aus diesen Erkenntnissen ein diagnostischer Marker, mit dem wir den Fortschritt der Erkrankung beim Patienten messen können?“, fragt Berens.

Mithilfe des Bernstein Preises will Berens nun eine Arbeitsgruppe an der Universität Tübingen aufbauen, wo er bereits ein Projekt am Bernstein Zentrum und dem Werner Reichardt Centrum für Integrative Neurowissenschaften – CIN (dem Exzellenzcluster der Universität) leitet und mehrere Kooperationspartner hat. Er freut sich auf die anstehenden Forschungsprojekte: „Die Herausforderung bei der Erforschung des Nervensystems ist, einen Bereich zu finden, der ausreichend komplex ist, dass dort auch etwas Spannendes passiert – aber gleichzeitig einfach genug, um ihn zu verstehen. Die Netzhaut ist ein ideales Beispiel dafür.“

Dr. Philipp Berens ist 1981 in Freiburg geboren und hat Bioinformatik (Diplom) und Philosophie (Bachelor of Arts) an der Universität Tübingen studiert. Von 2008 bis 2013 promovierte er bei Professor Dr. Matthias Bethge am Max-Planck-Institut für biologische Kybernetik in Tübingen und Professor Dr. Andreas Tolias am Baylor College of Medicine in Houston (USA). Für seine Dissertation über die Verarbeitung von Orientierungsreizen im Sehzentrum des Gehirns erhielt er die Bestnote summa cum laude. Ab Mitte 2012 bis Ende 2014 war er wissenschaftlicher Mitarbeiter in der Arbeitsgruppe von Professor Dr. Matthias Bethge am Bernstein Zentrum Tübingen. Seit November 2014 ist Berens Projektleiter unter Professor Dr. Matthias Bethge und Professor Dr. Thomas Euler am Bernstein Zentrum Tübingen und dem Universitätsklinikum Tübingen und ist weiterhin als Gastwissenschaftler im Labor von Professor Dr. Andreas Tolias am Baylor College of Medicine in Houston (USA) tätig. Berens gewann 2013 den Klaus Tschira Preis für verständliche Wissenschaft für die anschauliche Darstellung seiner Forschungsarbeit und wurde zweimal mit dem Lehrpreis für seine Tätigkeit an der Tübinger Graduiertenschule für Neurowissenschaften ausgezeichnet.

Der Bernstein Preis wird dieses Jahr bereits zum zehnten Mal verliehen und ist Teil des vom BMBF im Jahre 2004 ins Leben gerufenen Nationalen Bernstein Netzwerks Computational Neuroscience. Ziel der Förderinitiative war es, die neue Forschungsdisziplin in Deutschland nachhaltig zu etablieren. Inzwischen hat sich das Netzwerk mit Hilfe der BMBF-Förderung zu einem der größten Forschungsnetze im Bereich der Computational Neuroscience weltweit entwickelt. Namensgeber des Netzwerks ist der deutsche Physiologe Julius Bernstein (1835-1917).

Ein Porträtbild von Dr. Philipp Berens steht bereit zum Download - Bitte nennen Sie folgende Bildrechte: Wieland Brendel © CC-BY 3.0

Organization:

• Bernstein Center for Computational Neuroscience
• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Contact: Prof. Dr. Philipp Berens

Die Mopsfledermaus (Barbastella barbastellus) erbeutet hauptsächlich Nachtfalter, die Ultraschall hören können. Ihre Echoortungssignale sind jedoch so leise, dass die Insekten die Fledermaus erst wahrnehmen, wenn sie so nah dran ist, dass keine Zeit zur Flucht bleibt.

Die nach oben gerichteten und leisen Nasenlaute eignen sich bestens für den Fang hörender Nachtschmetterlinge, haben aber den Nachteil, dass keine Echos von der Umgebung unterhalb der Fledermaus zurückkomzurückkommen. Die Autoren der Studie vermuten, dass die nach unten gerichteten Laute evolviert wurden, um diesen Nachteil zu kompensieren. Die Mopsfledermäuse erhalten aus den Echos dieser Laute Informationen über die Umgebung unter ihnen. Dieses spezielle, bidirektionale und bifunktionale Echoortungssystem ist eine Anpassung an die Jagd auf Nachtfalter mit gutem Hörvermögen, meinen die Wissenschaftler.

Originalpublikation:
dx.plos.org/10.1371/journal.pone.0135590

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Reseach Group: Echolocation in Bats

Contact: Prof. Dr. Hans-Ulrich Schnitzler

However, there are times in which we focus on a single spot, for example when threading a needle. This requires tremendous focus of the eyes on the “eye” of the needle. But even during intense concentration on such a small point in space, the brain still keeps up awareness of the periphery, so we can react to anything happening in our broader field of view. Tübingen investigators led by Dr. Ziad Hafed (CIN) have now analysed data collected in concert with the team of Prof. Dr. Peter Thier (HIH) to uncover how this peripheral awareness functions: rather than completely eliminating all eye movements while focusing on the needle, the brain instead utilises tiny, almost imperceptible eye movements – mere fractions of a degree in size – in a big way. Hafed and his team found that these tiny eye movements have a large impact in “highlighting” sensory information in our periphery – even without us being aware of them.

These very small eye movements are called microsaccades. In contrast to normal saccades, which let us look at a new object or part of it in our field of view, microsaccades only result in what seem at first glance to be negligible readjustments. However, in their investigation, Dr. Hafed and his team were able to detect an increase in neuronal activity immediately before the occurrence of each microsaccade – evidence of heightened attention and a highlighting of the visual scene. Microsaccades follow a recognisable, quick rhythm, undulating several times per second. Even points far away from the eye’s focus are “highlighted” when microsaccades increase attention. This mechanism allows our brain to “keep an eye out” even when our actual eyes are busy, keeping tabs on the environment, warning of danger, and thus allowing our active perception to rapidly re-focus on anything that might happen.

The results uncovered by Hafed and his team potentially open the door for future engineering applications. For example, if computer interfaces were to track microsaccades of computer users with cameras, computers could predict when the users’ brains may be more or less “sensitized” to new stimuli. Such “smart” user interfaces could thus optimize on a millisecond basis when and where to provide visual feedback to their users to maximize work efficiency.

Publication: Chih-Yang Chen, Alla Ignashchenkova, Peter Thier & Ziad Hafed: Neuronal Response Gain Enhancement Prior to Microsaccades. Current Biology (2015), July 16th 2015 (online publication).

The brain constantly combines sensory inputs – the phone ringing – with the current behavioral context – expecting a call or listening to a concert – to choose an action. How does this work within the brain? Which brain regions encode the context, and which brain regions make the decision? Does a single region decide, or is it a network of brain regions? How is the decision relayed to the executing stages? The new study by Tübingen Neuroscientists gives important answers to these fundamental questions.

The researchers are able to show that decisions are not made in a single brain region, but that they evolve concurrently in a dense network of frontoparietal regions in the so-called association cortex. From there, neuronal choice signals are relayed not only to motor regions, which control behavioral responses, but also to sensory regions, which first encode the information that the choice is based on. Thus, choice signals are also fed back along the sensorimotor pathway to where sensory information is first processed. Furthermore, Siegel and his colleagues’ findings suggest that the frontoparietal association network is critical for neural processing of the behavioural context. During decision-making, context signals are broadcast from this network to other sensory and motor regions.

Thus, even simple behavioural decisions are based on a complex interplay of widely distributed brain regions. Answering or muting the phone as prompted by the current situation feels effortless and simple. But in our brain, a widely distributed network of brain regions does the heavy lifting in split seconds: sensory inputs are processed and assessed, inputs are combined with the current context, information is exchanged within the network – everything to finally initiate what feels to us like ‘the natural thing’ to do.

Publication: Markus Siegel, Timothy J. Buschman, Earl K. Miller: Cortical information flow during flexible sensorimotor decisions. Science (2015), 19. Juni 2015.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

The human brain consists of about 100 billion interconnected neurons, clustered in various functional regions. These regions fulfil different specific tasks, but are in constant communication with each other. These interactions between brain regions are the basis of our thoughts and actions. Disorders in these interactions, however, are often at the heart of neurological diseases, such as multiple sclerosis (MS).

To non-invasively investigate interactions between brain regions, neuroscience research is employing fMRI, which indirectly measures brain activity by monitoring blood flow and the blood’s oxygen levels in the brain. Nerve tissue uses a lot of energy – our brain consumes about 25% of our daily calories intake –, so active regions of the brain are better supplied with blood than their inactive counterparts. This leads to conclusions about which brain regions are currently “at work”  and interacting with other brain regions. However, since fMRI does not directly measure neuronal activity, but blood circulation and oxygenation, it remains unclear if and which neuronal interactions fMRI actually reflects.

To fill this knowledge gap, Dr. Siegel and his team correlated fMRI recordings of human subjects with their magnetoencephalography (MEG) measurements. In contrast to fMRI, MEG directly measures brain activity – it registers the tiny magnetic fields generated by neuronal activity. MEG has poorer spatial resolution than fMRI, but its exquisite temporal resolution allows for resolving different brain rhythms: fast, periodic changes in brain activity. Tübingen University is one of very few German institutions with an MEG facility.

Markus Siegel and his team compared the interactions between 450 points in the brain as measured with both fMRI and MEG. The team evaluated about 100,000 individual data points. This effort has paid off: they were able to show a direct relation between neuronal activity and neuronal interactions measured with fMRI. Moreover, they were able to show that that this relation is not the same across the brain. Instead, fMRI reflects interactions between different brain rhythms for different pairs of brain regions. Thus, much of the information provided by fMRI is complementary to that provided by MEG.

These findings provide an important fundament for the use of fMRI in neuroscience research. Furthermore, these results demonstrate the advantages to be gained by combining fMRI with its high spatial resolution and MEG or EEG with their high temporal resolution.  The combination of methods promises to be of use in diagnostics or even during preparation of therapy in the future. The new window will deliver ever clearer pictures of what happens in the healthy and diseased human brain.

Publication: Joerg F. Hipp, Markus Siegel: BOLD fMRI Correlation Reflects Frequency-Specific Neuronal Correlation. Current Biology (2015), May 18, 2015 (online publication).

dx.doi.org/10.1016/j.cub.2015.03.049

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

It has been known for quite some time that emotional reactions are in many cases an acquired habit of the brain. This happens through conditioning: a reaction is associated with a stimulus that wouldn’t normally prompt it. Pavlov’s famous dog, for instance, was fed when a bell rang. After a while, it started salivating whenever the bell rang, even in the absence of food. This mechanism has proved to be extremely useful during the course of evolution, which is why it is prevalent in all higher-developed species: animals have learned to be on their guard against certain sets of stimuli, to be afraid of them and instinctively do the right thing: keep their distance.

To persons suffering from posttraumatic stress or other anxiety disorders based in psychology, however, the automatism of fright is much less helpful. Perspiration, anxiety attacks, insomnia – these symptoms destroy the quality of life for persons who suffer from them. Therefore, neuroscientist seek a deeper understanding of what happens in the brain when it „learns the meaning of fear“. For anxiety, once learned, can indeed be un-learned by a process called extinction.

In the human brain, a comparatively tiny area performs the emotional evaluation of sensory stimuli: the amygdala, a part of the temporal lobe similar to almonds in size and shape, adds a so-called ‚emotional tag’ to our perceptions. Within the amygdala, fear is learned – and un-learned.  When certain combinations of sensory stimuli enter the amygdala, they stimulate excitatory neurons (nerve cells that excite many others) in the basolateral amygdala (BLA). These send and impulse to the central amygdala, which transmits an anxiety reaction to other areas of the brain. If this happens often, it increases the excitability and connectivity of these neurons.

The Tübingen research team led by Ingrid Ehrlich has now studied certain nerve cell clusters attached to the BLA known as medial paracapsular intercalated cells (mpITCs). For the first time, the team was able to prove that mpITCs receive not only excitatory impulses from the BLA, but also sensory stimuli. They then send an inhibitory impulse to the BLA’s excitatory cells, and to the central amygdala.

Moreover, mpITCs are capable of producing variable amounts of inhibition, directed at different parts of the amygdala, depending on the kind of stimuli they receive. They are thus a kind of relay station providing feed-forward or feed-back: an organisational unit exerting great influence on the immediacy and power of a learned anxiety reaction. Simply put: mpITCs are the gatekeepers of fear.

And what are the consequences of this, where the faint of heart are concerned? „As with all processes of learning, fear learning and extinction are extremely complicated“, says Ehrlich. „If there was just one simple mechanism, that would be where the development of treatments would start. But it is not that simple.“ But Ehrlich is still optimistic: „We are beginning to understand a huge number of things that have remained totally unclear until recently.“ Accordingly, the subject is causing quite a few ripples among experts at the moment. Almost simultaneously with the Tübingen research group, an team of Australian scientists carried out a comparable study. „It is almost a bit of a race“, Ehrlich says, „It’s downright exciting!“

Publication: Douglas Asede, Daniel Bosch, Andreas Lüthi, Francesco Ferraguti, Ingrid Ehrlich: Sensory Inputs to Intercalated Cells Provide Fear-Learning Modulated Inhibition to the Basolateral Amygdala. Neuron (2015), 2. April 2015 (online-Publikation), 22. April 2015 (Print-Publikation).

dx.doi.org/10.1016/j.neuron.2015.03.008.

Press release for download in German only. Pressemitteilung zum Download nur in Deutsch.

Obwohl das Gehirn bei weitem nicht die Schnelligkeit eines Computers erreicht, übertrifft es diesen in seiner Lernfähigkeit und seinem Erinnerungsvermögen. Grundlage dafür ist die flexible Vernetzung von über 100 Milliarden Nervenzellen. Eine wichtige Rolle spielen dabei Dornfortsätze, auch „dendritische Spines“ genannt. Diese feinsten Nervenzellausläufer werden beim Lernen und Erinnern stetig umgebaut. Die Veränderbarkeit neuronaler Signalübertragung ist eine der herausragenden Eigenschaften des Gehirns und wird von Neurowissenschaftlern als zelluläre Grundlage für das menschliche Gedächtnis angesehen.

Dies ist besonders einleuchtend, wenn man assoziatives Gedächtnis verstehen möchte. Dabei gilt es, Informationen, die auf den ersten Blick nichts miteinander zu tun haben, aufzunehmen, zu verknüpfen und als sinnvollen Zusammenhang zu speichern. Solche Verknüpfungen (oder Assoziationen) liegen auch den komplexesten Denkvorgängen zugrunde. „Nur wenn die beiden höchst unterschiedlichen Signale miteinander verknüpft werden, erfolgt ein Umbau an den Kontaktstellen der miteinander kommunizierenden Nervenzellen. Kurz gesagt: "Wir haben dann etwas gelernt“, erklärt Professor Cornelius Schwarz vom Hertie-Institut für klinische Hirnforschung und dem Werner Reichhardt Centrum für Integrative Neurowissenschaften der Universität Tübingen.

Damit die Forscher dem Gehirn der Mäuse beim Lernen zusehen konnten, trainierten sie diese auf eine einfache Lernaufgabe: Der Assoziation eines Berührungsreizes an ihren Tasthaaren mit einem darauffolgenden kleinen Luftstoß gegen die Augen. „Das Tasthaarsystem der Nager ist hierfür von herausragender Bedeutung, da die sensorischen Eingänge jedes einzelnen Tasthaars an einem sehr kleinen, aber gut bekannten Ort auf der Großhirnoberfläche verarbeitet werden“, sagt Schwarz. Während die Tiere lernten, ihre Augen nach der Tasthaarberührung zu schließen, um den Luftstoß aufs offene Auge zu vermeiden, haben die Hirnforscher starke Umbauvorgänge der Dornfortsätze beobachtet. Es wurden im Mittel 15 Prozent der Dornfortsätze abgebaut, je länger der Lernprozess voranschritt und je besser war die individuelle Lernleistung der Maus. Ein Hinweis auf die hohe räumliche Präzision der Assoziationsprozesse ist es, dass der Dornfortsatzumbau nur an dem Punkt der Großhirnoberfläche stattfand, wo der sensorische Eingang des fraglichen Tasthaares war.

„Die beobachteten, hochspezifischen Eigenschaften des Dornfortsatzumbaus und die große zeitliche Korrelation mit dem Lernerfolg geben großen Anlass zur Hoffnung, dass der damit verbundene Netzwerkumbau kausal für die langfristige Speicherung des Lerninhalts verantwortlich ist“, so Schwarz über die Ergebnisse der Studie. Mit diesen Beobachtungen ist es den Wissenschaftlern gelungen, eine Tür zum Verständnis der Mechanismen des assoziativen Lernens aufzustoßen. Noch ist nicht klar, ob alle Zelltypen des Großhirns solche Veränderungen aufzeigen und warum der von den Forschern beobachtete Zelltyp einen Abbau von Nervenzellverbindungen aufzeigt und nicht einen Aufbau. Auch sind die physiologischen Signale unbekannt, die zu einer solchen Verknüpfung mit darauffolgendem Dornfortsatzumbau führen. All dies muss in weiteren Experimenten aufgeklärt werden.

Viele Gehirnkrankheiten, wie Schizophrenie, Alzheimer und Parkinson sind durch Beeinträchtigungen des Großhirns und damit des Denk- und Lernvermögens charakterisiert. Bevor die Verbesserung dieser Symptome und ihrer zugrundeliegenden neuronalen Prozesse ins Visier genommen werden können, müssen dieselben Prozesse im gesunden Gehirn verstanden worden sein. Auf diesem Weg sind die Tübinger Forscher ein kleines, aber wichtiges Stück weiter gekommen.

Übertragbarkeit der Ergebnisse auf den Menschen:Das Großhirn ist ein Wunderwerk an dicht miteinander verschalteten Nervenzellen, die über der gesamten Oberfläche unseres Großhirns in sich wiederholenden Einheiten mit nahezu identischem Verschaltungsplan vorliegen. Die Teile des Denkorgans arbeiten daher sehr wahrscheinlich nach demselben Schema, ob diese nun mit Signalen aus den Sinnesorganen, Kommandos zur Bewegung der Muskeln oder abstrakteren Denkvorgängen umgehen. Interessanterweise gilt diese Ähnlichkeit auch für den Aufbau der Großhirne beim Vergleich zwischen Säugetieren. Die Speziesunterschiede im mikroskopischen Aufbau dieses Organs sind winzig. Die höheren Denkleistungen des Menschen scheinen daher nicht durch eine „genialere Verschaltung“ im Großhirns, sondern lediglich durch die massivere Akkumulation von ähnlich aufgebauten Netzwerkeinheiten und damit die Möglichkeit der Repräsentation von noch mehr und noch abstrakteren Denkeinheiten getragen zu sein. Die Ähnlichkeit zwischen Spezies macht es möglich, dass durch das Studium von tierischen Gehirnen wichtige Erkenntnisse über menschliche Denkleistungen zu Tage gefördert werden können.

Originalpublikation: Joachimsthaler, B., Brugger, D., Skodras, A., Schwarz, C. (2015): Spine loss in primary somatosensory cortex during trace eyeblink conditioning. Journal of Neuroscience 35: pp. 3772-378.

Organization:

• Hertie Institute for Clinical Brain Research
• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Systems Neurophysiology

Contact: Prof. Dr. Cornelius Schwarz

The paper, “Open Labware: 3-D Printing Your Own Lab Equipment,” describes the innovative paths taken by two organisations of neuroscientists – Teaching and Research in Natural Sciences for Development (TReND) in Africa and Backyard Brains in Latin America – to help produce a remedy. Drawing on recent technological and cultural advances, they organise workshops and summer schools to teach aspiring young researchers a Do-It-Yourself (DIY) approach to Neuroscience. This “Open Labware” approach is based on ever-increasing interactions between scientific communities and the global “maker movement”. DIY- and Open Source-inspired “makers” have long been utilising 3D printing and other developments in electronic technology to design and build their own technical solutions. Lab equipment can be made affordable this way, too.

Instruments like micropipettes, manipulators and microscope adapters can easily be assembled from 3D printed plastic parts and materials readily available in any given general store. The benefits of this approach are twofold: the quality of these appliances is good enough to perform many basic experiments and a worldwide culture of sharing assures that any kinks and flaws are quickly identified and removed by the community. Furthermore, many designs undergo a rapid evolution as each user adapts them to their own specific needs. Making one’s own lab tools also contributes to a better understanding and empowered usage.

This development, and the steep decline in 3D printer prices, makes “Open Labware” particularly attractive for developing countries such as Uganda and Tanzania in Africa, and Chile and Mexico in Latin America. TReND and Backyard Brains teach the programming and basic electronics skills needed and have held over 100 (neuro-)science outreach events, science camps, workshops and lectures, with more than 10,000 students, parents and teachers enthusiastically taking part. Tübingen neuroscientist Baden (Werner Reichardt Center for Integrative Neuroscience – CIN) of TReND and his colleagues recommend integrating more aspects of the design and use of Open Labware into science curricula, and making 3D printing readily available at schools and universities. If the widespread lack of expertise in using these low-cost, high-efficiency technologies can be overcome, they expect the maker movement to make substantial contributions not just in neuroscience but in other resource-intensive life science fields.

Publication: Baden T, Chagas AM, Gage G, Marzullo T, Prieto-Godino LL, Euler T (2015): Open Labware: 3-D Printing Your Own Lab Equipment. PLoS Biology 13(3): e1002086.

dx.doi.org/10.1371/journal.pbio.1002086

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

Wie die Tiefe Hirnstimulation genau wirkt, vermag die Medizin bis heute nicht sicher zu sagen. Neue Erkenntnisse zu den Grundlagen der Parkinson-Krankheit und zur Funktionsweise der Tiefen Hirnstimulation sind aber wertvoll, um die Therapie fortlaufend weiter zu entwickeln.

Die Forschergruppe um Dr. Daniel Weiss und Professor Alireza Gharabaghi am Werner-Reichardt-Centrum für Integrative Neurowissenschaften (CIN) der Universität Tübingen stellt nun einen direkten Zusammenhang zwischen der Tiefen Hirnstimulation und den (patho)physiologischen Grundlagen der Parkinson-Krankheit her. Die Forscher untersuchten anhand von Hirnströmen (nicht-invasiv und schmerzfrei durch Oberflächen-EEG auf der Kopfhaut gemessen), wie sich die Tiefe Hirnstimulation des Nucleus Subthalamicus auf die Verschaltung und Kommunikation von Neuronengruppen des Großhirns (Kortex) auswirkt. Sie stellten fest, dass die Tiefe Hirnstimulation des Nucleus Subthalamicus die Verarbeitung von Bewegung im Großhirn wesentlich unterstützen und stärken kann. Zudem konnten die Forscher zeigen, dass die verbesserte Leistung des Großhirns auch geeignet war, um die motorische Verbesserung der Patienten durch die Tiefe Hirnstimulation vorherzusagen. Die Normalisierung der Großhirnfunktion bei der Parkinson-Krankheit scheint also eng mit der motorischen Verbesserung verknüpft zu sein. Zudem konnten die Forscher in Zusammenarbeit mit dem US-amerikanischer Forscher Dr. Govindan zeigen, dass die Tiefe Hirnstimulation des Nucleus Subthalamicus Hirnareale dämpft, die bei der Parkinson-Krankheit übermäßig hemmend auf Bewegungsplanung und -ausführung wirken.

Die Tübinger Forscher haben damit in ihrer Arbeit wesentliche neue Funktionsmechanismen der vielfach mit sehr gutem Erfolg eingesetzten Tiefen Hirnstimulation nachgewiesen. Über das Grundlagenverständnis der Therapiemechanismen hinaus, beinhaltet die Arbeit wertvolle Hinweise, um die Tiefe Hirnstimulation noch besser für die individuellen Bedürfnisse der Patienten zu optimieren. Diese und weitere elektrophysiologische Biomarker können in Zukunft dazu dienen, die Tiefe Hirnstimulation noch effektiver und gezielter einzusetzen.

Optimaler Weise könnten aus der elektrischen Hirnaktivität Parkinsonsymptome bereits vorhergesagt werden, bevor sie wenige Sekunden später für den Patienten fassbar einsetzen – in der Regel gehen nämlich Anpassungen der Hirnaktivität den motorischen Symptomen und Leistungen voraus. Die optimale Stimulation der Zukunft würde also bereits dann einsetzen, wenn die Nervenzellaktivität zwar bereits eine klinische Verschlechterung vorhersagt, diese aber noch durch elektrische Impulse behandelt werden kann, bevor sie für den Patienten überhaupt spürbar wird.

Publikation: Daniel Weiss, Rosa Klotz, Rathinaswamy B. Govindan, Marlieke Scholten, Georgios Naros, Ander Ramos-Murguialday, Friedemann Bunjes, Christoph Meisner, Christian Plewnia, Rejko Krüger, Alireza Gharabaghi (2015): Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson’s Disease. Brain: A Journal of Neurology, 1–15, 2. Januar 2015.

Organization:

• University Hospital Tübingen
• Hertie Institute for Clinical Brain Research
• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neuroprosthetics

As photographers will know, there is a very substantial difference between the sky and the ground in terms of brightness and contrast. On the ground average brightness is rather low in comparison with the sky, and light is reflected from things such as leaves and the earth, so that contrasts of bright and dark are roughly equally frequent. Light from the sky, however, is usually direct, with objects appearing as dark silhouettes against a bright background. So it would make sense for different parts of the eye to be adapted to the predominant distribution of contrast below and above the horizon.

“Indeed, this is the case: Green cones in the mouse retina respond similarly to dark and light stimuli, but blue cones respond more strongly to dark ones”, clarifies the scientist. The ‘blue’-sensitive, sky-oriented lower half of the mouse retina is tuned to spot dark objects against a bright background. These objects can be, for example, birds of prey. The results match very well with two recent studies in which it was shown that mice either freeze or run and hide as soon as something dark appears above them. This instinctive reaction occurs within less than 200 milliseconds, which is too short a time to allow for a thorough ‘assessment’ of the situation. Therefore, the researchers think that this behavior is based on very fast visual processing, as it might be provided by a signal path specializing in dark contrasts that begins at the first synapse, with the cones.

Publication: Tom Baden, Timm Schubert, Le Chang, Tao Wei, Mariana Zaichuk, Bernd Wissinger, Thomas Euler (2013): A Tale of Two Retinal Domains: Near-Optimal Sampling of Achromatic Contrasts in Natural Scenes through Asymmetric Photoreceptor Distribution. Neuron 80, 1–12, December 4, 2013.

dx.doi.org/10.1016/j.neuron.2013.09.030

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

However, one also comes up against limits with this method. Human vision normally deals well with extreme contrasts of light levels in the environment: we are able to see in anything from weak starlight to glaring sunshine. In contrast, ‘optogenetic vision’ with channelrhodopsins would only work in the very brightest sunlight – at least with the variants of channelrhodopsin that have been developed so far.

Improving the characteristics of channelrhodopsins is something to be hoped for, above all from the point of view of developing potential future applications in humans. The researchers used a computer model they themselves developed to investigate how to achieve these improvements. This model makes it possible to assess how well different variants of channelrhodopsin would support restoring a sense of vision. “When one of these molecules is activated by light, it cycles through a defined set of states which ultimately determine the light response of the treated eye”, explains Marion Mutter. Previously, improvements to channelrhodopsin were mainly pursued to carry out research into basic neurobiological questions. “Our results show that optogenetic vision would benefit from completely different improvements which have so far been overlooked,” according to Marion Mutter and Thomas Münch.

What effects would these improvements have on the sense of vision? “According to our calculations, it should be possible to see in brightness conditions that are hundred-fold dimmer than what would currently be possible”, explains Thomas Münch, leader of the project. According to his estimates, this would allow patients treated with optogenetic techniques to be able to see not only in sunlight, but also in a well lit room. “At these brightness levels we reach the biophysical limits of what is possible with classical channelrhodopsin molecules”, says Münch. “However, in our study we could also show why there are these limits, and so we provide a direction for novel types of improvements in the future.”

Press release for download only in German. Pressemitteilung zum Download nur in Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Bernstein Center for Computational Neuroscience

Reseach Group: Retinal Circuits and Optogenetics

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Retinal Circuits and Optogenetics

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Bernstein Center for Computational Neuroscience

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

A new study published this week in the journal “Behavioral Neuroscience” is based on this effect. The visual performance of mice was examined using a chamber whose walls were made of four computer screens. The monitors showed a rotating striped pattern. This simulated movement of the environment triggered the optokinetic reflex and the mouse followed the pattern with its gaze – but only when the animal could recognize the striped pattern. This allows the visual performance of each individual animal to be determined. Just as the ophthalmologist can make the displayed pattern finer during vision testing, so too can the displayed pattern be changed until the animal is no longer able to recognize it and subsequently fails the reflex test.

The utilization of the computer monitors allows the contrast or resolution of the pattern to be changed in almost any way desired. For the study, doctoral candidate Boris Benkner has developed software that automatically evaluates the animal’s behavior and can thus determine the visual ability of an animal in a short time. “In previous studies, it was necessary to tediously analyze each animal’s behavior manually,” said Benkner. “Our automated method is not only faster but also more objective, because the stripe pattern does also influence the observer when doing the analysis.”

The senior author of the study, Thomas Münch, sees great potential in the newly developed method to evaluate new treatment strategies for blindness. “Currently, many new ways for treating blindness are being developed, ranging from dietary supplements to optogenetics to stem cell therapy” said Münch. “It is important to scrutinize these therapies from the beginning, to test if they really improve the visual abilities of the treated animals.”

Publication: Boris Benkner, Marion Mutter, Gerrit Ecke, and Thomas A. Münch (2013): Characterizing Visual Performance in Mice: An Objective and Automated System Based on the Optokinetic Reflex. Behavioral Neuroscience, Online First Publication, Aug. 20, 2013.

dx.doi.org/10.1037/a0033944

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Retinal Circuits and Optogenetics

Durch "zufällige und glückliche Umstände" (Varjú) geriet er an das berühmte Institut für Physikalische Chemie in Göttingen. Er fand bald, dass die Biologie, hier die Systemanalyse biologischer Reiz-Reaktions-Beziehungen, interessanter war als die bisherige Experimentalphysik. Schon 1958 wurde er mit einer Arbeit über Phototropismus und Licht-gesteuertes Wachstum des Algenpilzes Phycomyces in Physik promoviert. Er folgte Werner Reichardt (nach dem jetzt in Tübingen das CIN benannt ist) an die Abteilung 'Kybernetik' des Max-Planck-Instituts für Biologie in Tübingen, 1959/60 arbeitete er über Phycomyces am California Institute of Technology bei Max Delbrück. Auch Delbrück hatte als Physiker in Berlin begonnen, war in die USA emigriert und später zur Biologie gekommen.

Varjú erhielt einen Ruf nach Köln und 1968 einen Ruf auf einen Lehrstuhl für Zoologie (später 'Biokybernetik') in Tübingen.

Seit 1967 war er deutscher Staatsbürger. Im Jahre 1962 heirateten Dezsö Varjú und Heide Agner, eine Enkelin von Wilhelm Singer, der 1910 bis 1946 als Stadtpfleger für die Finanzen der Stadt Tübingen verantwortlich war. Im vorigen Jahr konnten die Eheleute die goldene Hochzeit feiern.

Der neue Zoologe entfaltete eine rege Tätigkeit. Sein Ziel war die Aufklärung der Sinneswahrnehmung und der Verhaltensreaktionen von Organismen und deren Beschreibung durch mathematische und computergestützte Modelle. Sein Lehrbuch der Systemtheorie für Biologen erschien 1977. Die 'etablierten' Labortiere waren Stubenfliege und Mehlkäfer, aber Varjú war fasziniert von der Vielfalt der wirbellosen Tiere. Er erforschte das Sehen von Strandkrabben und Schnecken, den Flug des Taubenschwänzchens, die Kreisbahnen der Taumelkäfer, den Beutefang von Wasserläufern, die erkennen, ob eine Schwingung der Wasseroberfläche von einer zappelnden Fliege herrührt.

Varjú hat Generationen von Tübinger Studenten in sein Forschungsgebiet Biokybernetik zwischen den Neurowissenschaften und der Verhaltensforschung eingeführt, bevor es den Begriff der Neuroethologie¸überhaupt gab. Einige seiner Schüler arbeiten erfolgreich weiter in diesem Gebiet. Er hatte besonders enge Bindungen nach Australien; dort verbrachte er einige Forschungsaufenthalte. Er war mehrfach Dekan der biologischen Fakultät.

Nach der Emeritierung 1997 hat Varjú seine Einsichten in einem sehr lesbaren  Buch allgemein zugänglich gemacht. In 'Mit den Ohren sehen und den Beinen hören' (mit Bezug auf Eulen und Heuschrecken) erklärt er, wie Wespen in Minuten den Erdbeerkuchen entdecken, und vieles andere zu Orientierung und Wanderungen von Tieren.

In den letzten Jahren galt sein Interesse der Frage, wie Tiere (z.B. Bienen, Krebse, Fische, Kaulquappen, Vögel) die Polarisation des Sonnenlichts zur Orientierung nutzen. Die Monographie 'Polarized Light and Animal Vision' mit Gábor Horváth aus Budapest erschien 2003.

Ein Zentrum im Leben von Dezsö und Heide Varjú war ihr Gütle in Kiebingen, wo sie so gern Gastgeber für Freunde und Verwandte waren. Varjús Engagement für Andere spiegelt sich wider in der Stiftung eines Preises für wissenschaftlich begabte Schüler seines Heimatlandes.

Dezsö Varjú wird in Erinnerung bleiben durch seine Arbeiten zum Bewegungssehen der Tiere und zu den Grundlagen der Biokybernetik.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

Organization:

• University Hospital Tübingen

Brochure for download in English and German. Broschüre zum Download in English and German.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Physiology of Active Vision

Contact: Prof. Dr. Ziad Hafed

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Ophthalmic Research

Contact: Prof. Dr. Thomas Euler

Press release for download only in German. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University Hospital Tübingen

Reseach Group: Retinal Degeneration

Contact: Prof. Dr. Dr. h.c. mult. Eberhart Zrenner

Press release for download in English only. Pressemitteilung zum Download nur auf Englisch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

In Japan Bälz is regarded not only as a major figure in the development of modern medicine, but also as a significant cultural figure. A monument to him that carries a dedication from the Japanese medical association stands outside the Casino restaurant on the Scharrenberg campus of the University clinic. On their visit to the CIN the NIPS delegation asked to see the tribute to Bälz – here they are photographed beside the Japanese-style memorial to the German doctor who spent his career in their country.

CIN Chairman Peter Thier commented: ‘It’s remarkable that every day so many people pass by this monument on their way to lunch at the canteen without noticing it at all. But to our visitors from Japan he is a very important figure, and they specially asked to pay their respects to Erwin Bälz.’

The visit to the Schnarrenberg campus was part of a programme of events to mark the signing of an agreement between the NIPS and the CIN, which was formalized in a ceremony on Friday November 30 attended by senior figures from both institutes, as well as by President of the University of Tübingen Berndt Engler, as well as by representatives of the Deutsche Forschungsgemeinschaft and the Japanese Society for the Promotion of Science. The planned cooperations will involve joint funding applications as well as the exchanging of scientists and students.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

Press release for download only in German. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Press release for download only in German. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

Press release for download only in German. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research

Reseach Group: Computational Sensomotorics

Contact: Prof. Dr. Martin A. Giese

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Max Planck Institute for Biological Cybernetics

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Press release for download only in German. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Neural Basis of Visual Behavior

Contact: Dr. Steffen Katzner

Press release for download in German only. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Reseach Group: Computational Neuroscience

Contact: Prof. Dr. Matthias Bethge

Press release for download in German only. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Press release for download in German only. Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Large-Scale Neuronal Interactions

Contact: Prof. Dr. Markus Siegel

Press release for download in English only. Pressemitteilung zum Download nur auf Englisch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Vision and Cognition

Contact: Prof. Dr. Andreas Bartels

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• University of Tübingen
• University Hospital Tübingen

Press release for download in English only. Pressemitteilung zum Download nur auf Englisch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Max Planck Institute for Biological Cybernetics
• University of Tübingen
• University Hospital Tübingen
• Hertie Institute for Clinical Brain Research
• Bernstein Center for Computational Neuroscience

Contact: Prof. Dr. Matthias Bethge

Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Computational Neuroscience

Contact: Prof. Dr. Matthias Bethge

Organization:

• Werner Reichardt Centre for Integrative Neuroscience
• Hertie Institute for Clinical Brain Research
• University Hospital Tübingen

Reseach Group: Computational Sensomotorics

Contact: Prof. Dr. Martin A. Giese

Pressemitteilung zum Download nur auf Deutsch.

Organization:

• Werner Reichardt Centre for Integrative Neuroscience

Reseach Group: Retinal Circuits and Optogenetics

Pressemitteilung zum Download nur auf Deutsch.

Organization:

• University of Tübingen
• Werner Reichardt Centre for Integrative Neuroscience

Pressemitteilung zum Download nur auf Deutsch.

Organization:

• University of Tübingen
• Werner Reichardt Centre for Integrative Neuroscience

Pressemitteilung zum Download nur auf Deutsch.

Organization:

• University of Tübingen
• Werner Reichardt Centre for Integrative Neuroscience