A major goal of modern neuroscience is to identify how and where in the brain experience modifies synapses. Such knowledge would advance the understanding and treatment of major neurological and neuropsychiatric diseases, such as post-traumatic stress disorder, schizophrenia, dementia and substance abuse disorders. The general goal of this grant has been to understand the nature of synaptic changes triggered by brief conditioning periods of synaptic activity (such as long-term potentiation, LTP; and long-term depression, LTD) and determine their functional consequences. In this grant period, we will focus on the role that LTP and LTD play in associative memory. In particular, we will test the hypothesis that modification of synapses by LTD and LTP can turn off and subsequently turn back on a previously established associative memory. Such experiments will investigate the causal role between these well-studied cellular processes and memory.

Public Health Relevance

This project seeks to understand the basic cellular and molecular mechanisms underlying memory processes. It is hoped that such understanding will eventually enable better treatment of neurological and neuropsychiatric diseases such as post-traumatic stress disorder, schizophrenia, dementia and substance abuse disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH049159-28
Application #
9210652
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Asanuma, Chiiko
Project Start
1992-05-01
Project End
2020-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
28
Fiscal Year
2017
Total Cost
$447,944
Indirect Cost
$155,104
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Alfonso, Stephanie I; Callender, Julia A; Hooli, Basavaraj et al. (2016) Gain-of-function mutations in protein kinase C? (PKC?) may promote synaptic defects in Alzheimer's disease. Sci Signal 9:ra47
Malinow, Roberto (2016) Depression: Ketamine steps out of the darkness. Nature 533:477-8
Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D et al. (2016) Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice. Biol Psychiatry 80:827-835
Dore, Kim; Aow, Jonathan; Malinow, Roberto (2016) The Emergence of NMDA Receptor Metabotropic Function: Insights from Imaging. Front Synaptic Neurosci 8:20
Reinders, Niels R; Pao, Yvonne; Renner, Maria C et al. (2016) Amyloid-? effects on synapses and memory require AMPA receptor subunit GluA3. Proc Natl Acad Sci U S A 113:E6526-E6534
Aow, Jonathan; Dore, Kim; Malinow, Roberto (2015) Conformational signaling required for synaptic plasticity by the NMDA receptor complex. Proc Natl Acad Sci U S A 112:14711-6
Dore, Kim; Aow, Jonathan; Malinow, Roberto (2015) Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow. Proc Natl Acad Sci U S A 112:14705-10
Nabavi, Sadegh; Fox, Rocky; Alfonso, Stephanie et al. (2014) GluA1 trafficking and metabotropic NMDA: addressing results from other laboratories inconsistent with ours. Philos Trans R Soc Lond B Biol Sci 369:20130145
Nabavi, Sadegh; Fox, Rocky; Proulx, Christophe D et al. (2014) Engineering a memory with LTD and LTP. Nature 511:348-52
Kessels, Helmut W; Nabavi, Sadegh; Malinow, Roberto (2013) Metabotropic NMDA receptor function is required for ?-amyloid-induced synaptic depression. Proc Natl Acad Sci U S A 110:4033-8

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