My long-term goal for an independent research career is to carry forward the understanding of the central auditory system physiology and the molecular mechanisms that underlie its plasticity. Defects in this system may cause several diseases such as auditory neuropathies, tinnitus or impairments in language understanding. For this long-term purpose, I will do my post-doctoral experience in the laboratory of Pr. Schneggenburger (Brain Mind Institute/Ecole Polytechnique Fédérale de Lausanne/Switzerland) who is a world specialist in the study of the calyx of Held, a model synapse that belongs to the brainstem auditory pathway. The overall objective of this proposal is to gain insight into the molecular cues that determine the formation of the large calyces of Held synapses in the auditory brainstem. Calyces of Held are large excitatory glutamatergic synapses of the superior olivary complex, which rapidly relay information on sounds arriving at the contralateral ear. They thus play a role in sound source localization. Despite their important function, the molecular mechanisms which guarantee the correct formation of these synapses during development are unknown. In this project, we will therefore seek to answer the following two questions: 1) What are the molecular mechanisms that guarantee the formation of large calyces of Held synapses on the contralateral side of the brain, 2) What is the role of the Wnt signaling pathway in axon remodeling that ultimately leads to the formation of the large calyx of Held synapse.
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