Werner Reichardt Centrum für Integrative Neurowissenschaften (CIN)

17.04.2015

Press Release: Teaching the Brain the Meaning of Fear

Teaching the meaning of fear – that is no empty phrase, as Tübingen neuroscientists discover more and more clearly. A research group led by Ingrid Ehrlich (Werner Reichardt Centre for Integrative Neuroscience [CIN] / Hertie Institute for Clinical Brain Research [HIH]) studies mechanisms of conditioned learning – especially with regard to emotional memory – on a cellular level.

Recently, they took a large step towards a better understanding of fear reactions. The group examined nerve cell clusters in mouse brains that had up to now been little understood, and that furthermore have direct analogues in the human brain. These clusters fulfill a gatekeeper function in learning and un-learning persistent fear. The Tübingen researchers have now published their findings in the esteemed scientific journal ‚Neuron’.

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.

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