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.

Public Health Relevance

Changes in the strength of communication among neurons underlie learning and memory. Abnormal modulation of neuronal communication can result in psychiatric disorders such as schizophrenia, depression, and post-traumatic stress disorder. Insights into the mechanisms of learning and memory in health and disease will be gained by studying calcium-sensing proteins, such as synaptotagmins, that regulate this process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32MH100752-01A1
Application #
8647667
Study Section
Special Emphasis Panel (ZRG1-F03A-N (20))
Program Officer
Li, Ingrid Y
Project Start
2013-12-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
1
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305