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Max-Planck-Gesellschaft
Max-Planck-Institut für Experimentelle Medizin
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Dr. Sonja Wojcik

Vesicular Transporters; Functional Analysis of Inhibitory and Excitatory Neurotransmitter Systems

 

Neurons communicate by translating an electrical signal into the release of neurotransmitter at synaptic contacts, to either activate or inhibit the postsynaptic neuron. The balance between excitation and inhibition is essential for brain function, and imbalances are thought to play a role in neurological disorders as divergent as epilepsy and schizophrenia. We are using genetic mouse models to analyze the process of neurotransmitter release in excitatory neurons that release glutamate as well as in their inhibitory counterparts that use GABA or glycine as neurotransmitters. Shutting down neurotransmitter release throughout the brain by global genetic deletion of essential synaptic proteins has surprisingly little effect on either the basic molecular assembly of synapses or the initial development of overall brain architecture. Developmental processes that are affected by synaptic activity are likely to depend on competition between active and inactive neurons and are therefore better studied by silencing  only subsets of neurons in the brain.

In this context the inhibitory, GABAergic neurons are particularly interesting, because GABA signaling has been implicated in neuronal maturation and network development as well as in the integration of newborn neurons into established networks. Furthermore, the great diversity of GABAergic interneuron types, which can be distinguished based on their morphological features, electrophysiological properties and protein expression profiles presents a complex picture, but also lends itself to very selective genetic intervention. In particular, the combination of interneuron subtype specific Cre-recombinase expression with a conditional knockout allele of the vesicular inhibitory amino acid transporter will allow the selective inactivation and analysis of defined network components.

In addition to studying the role of neurotransmitter release in synaptic and nervous system development, we are also interested in the basic molecular processes of vesicle fusion. We are currently studying regulatory proteins that control vesicle fusion in neurons and neuroendocrine cells, as well as vesicular transporters, who in addition to their main task of filling synaptic vesicles have cell biological functions that affect vesicle size, shape and cycling.



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