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Neural communication in the adult nervous system is mediated primarily through chemical synapses, where action potentials elicit Ca2+ signals, which trigger vesicular fusion and neurotransmitter release in the presynaptic compartment. At early stages of development, the brain is shaped by communication via trophic factors and other extracellular signalling, and by contact-mediated cell–cell interactions including chemical synapses. The patterns of early neuronal impulses and spontaneous and regulated neurotransmitter release guide the precise topography of axonal projections and contribute to determining cell survival. We study of the role of specific proteins of the synaptic vesicle release machinery in the establishment, plasticity, and maintenance of neuronal connections during development. We examine mouse models where various members of the N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex have been genetically manipulated (e.g. Snap25 or Munc13). We are focusing on the role of regulated vesicular release and/or cellular excitability in synaptic assembly, development and maintenance of cortical circuits, cell survival, circuit level excitation–inhibition balance, myelination, refinement, and plasticity of key axonal projections from the cerebral cortex. These models are important for understanding various developmental and psychiatric conditions, and neurodegenerative diseases.

These projects are in collaboration with the groups of Professor Mann, Professor Vyazovskiy and involve collaborations from Charité, Berlin and MPI, Göttingen.


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