Uni-Tübingen

P9: cGMP pathways as novel molecular targets in the brain for autistic, cognitive and auditory processing disabilities

Aims

To determine whether cGMP signaling cascades are perturbed in the brains of mouse models of learning impairments, auditory processing deficits and autism. We moreover aim to investigate to what extent cGMP-modulating drugs may correct these disabilities.

Questions and Methods

cGMP and the Brain

Boston Internship

Jacob Lab

In the Jacob lab in Boston, the doctoral researchers will

  1. translate molecular expertise in cGMP signaling to test for altered levels of this pathway in APC conditional KO mice,
  2. learn to quantitatively assess synaptic spine density and structural maturation using high-resolution confocal microscopy techniques, and
  3. be trained in diagnostic behaviors designed specifically to test for cognitive and autistic-like behaviors in mice.

Boston Co-mentor

Prof. Michele Jacob, PhD

Link to boston researcher lab

Doctoral Student

Philine Marchetta

Philine Marchetta studied biology at the University of Tübingen and earned her Bachelor’s degree in 2016 in the department of Animal Physiology. She went to Marburg to study Molecular and Cellular Neuroscience for her master’s and earned her degree in 2018. Her thesis was in the field of molecular neurophysiology with cooperation to the University Hospital of Tübingen. During her doctoral studies in the laboratory of Marlies Knipper in the department of Molecular Physiology of Hearing she will focus on the influence of cGMP pathways in the brain, especially the auditory processing but also cognition, plasticity and disorders such as autism spectrum. She is interested in electrophysiological methods as well as imaging and behavioral tests.


Key Publications

Chumak T, Rüttiger L, Lee SC, Campanelli D, Zuccotti A, Singer W, Popelar J, Gutsche K, Geisler HS, Schraven SP, Jaumann M, Panford-Walsh R, Hu J, Schimmang T, Zimmermann U, Syka J, Knipper M. BDNF in lower brain parts modifies auditory fiber activity to gain fidelity but increases the risk for generation of central noise after injury. Mol Neurobiol. 2016;53:5607-27

Jaumann M, Dettling J, Gubelt M, Zimmermann U, Gerling A, Paquet-Durand F, Feil S, Wolpert S, Franz C, Varakina K, Xiong H, Brandt N, Kuhn S, Geisler HS, Rohbock K, Ruth P, Schlossmann J, Hutter J, Sandner P, Feil R, Engel J, Knipper M, Ruttiger L. cGMP-Prkg1 signaling and Pde5 inhibition shelter cochlear hair cells and hearing function. Nat Med. 2012;18:252-9