Role of Synaptotagmins in Synaptic Plasticity in the Hippocampus

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DESCRIPTION (provided by applicant): Learning and memory requires use-dependent changes in synaptic function and transmission, a process known as synaptic plasticity. Many mental disorders such as schizophrenia, depression, and post-traumatic stress disorder may be linked to abnormalities in synaptic plasticity. One leading model of synaptic plasticity is long-term potentiation (LTP), which proposes that NMDA receptor activation enhances AMPA receptor mediated transmission to increase the strength of excitatory synapses. Despite decades of research, many aspects of the molecular mechanism underlying LTP remain unclear. The proposed study will test the hypothesis that calcium binding proteins known as synaptotagmins regulate the trafficking of AMPA receptors to the postsynaptic membrane. Presynaptic synaptotagmins are known to bind calcium and trigger neurotransmitter release. This study will use in vivo viral-mediated knockdown and replacement of synaptotagmins in CA1 pyramidal cells of the hippocampus. Electrophysiological recordings will be performed in acute hippocampal slices to determine the effect of these manipulations on LTP and basal transmission. Overall, these experiments will elucidate mechanisms of postsynaptic membrane trafficking and how they are involved in synaptic plasticity. Understanding these mechanisms may one day lead to new treatments for a variety of psychiatric disorders.