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Milstein Lecture- Molecular Mechanisms of Synaptic Transmission

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Thomas Sudhofs research investigates how neurons in brain communicate with each other during synaptic transmission, which is the process that underlies all brain activity, from simple reflexes to consciousness and memory. When stimulated, a presynaptic neuron releases neurotransmitters diffuse across the synaptic cleft to stimulate postsynaptic receptors. Synaptic transmission is initiated by neurotransmitter release, and completed with the postsynaptic response. However, synaptic transmission is more than just the transfer of information between neurons-synaptic transmission also processes the transferred information. Each synapses integreates temporal and spatial information and is plastic. As a result, synapses are naocomputers that remember previous events and that constitutes the minimal information processing unit in brain. Thomas Sudhofs laboratory studies three related questions about synapses: How are presynaptic and postsynaptic components of a synapse organized in molecular terms to allow rapid transfer of information, including ultrafast release of neurotransmitters? How is synaptic plasticity achieved? And finally, how is a synapse formed, specified and maintained or eliminated in a circuit-specific fashion? The talk will focus on the first question, and specifically describe the molecular machines that allow pre- and postsynaptic function and enable plasticity of release. The talk will revolve around one particular family of molecules, calcium-binding proteins called synaptotagmins, that are master organizers of pre- and postsynaptic membrane traffic, and will discuss recent results that provide insight into the intricate nanoarchitecture that allows a synapse to function rapidly and precisely.

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