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.
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.
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|Malinow, Roberto (2016) Depression: Ketamine steps out of the darkness. Nature 533:477-8|
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|Dore, Kim; Aow, Jonathan; Malinow, Roberto (2016) The Emergence of NMDA Receptor Metabotropic Function: Insights from Imaging. Front Synaptic Neurosci 8:20|
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|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|
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