The long-term goals of our research are to understand the molecular and cellular mechanisms of learning and memory in the brain. This application will focus on memory retrieval, a fundamental yet mysterious component believed to involve a rapid reconstructive process involving a new recapitulation of the learned information. Over the past several years, conditional gene knockout techniques have been shown to be increasingly valuable for molecular analysis of learning and memory processes. However, because these available techniques either lack temporal controls or only offer limited temporal resolutions, the molecular manipulations and analyses of memory retrieval process have not been rigorously attempted. This proposal will take advantage of our newly developed fourth-generation genetic technology that permits high time-resolution manipulations and analyses of the memory retrieval process. A comprehensive set of biochemical, genetic, and behavioral experiments will be conducted to demonstrate that memory retrieval, like other stages of memory process, can be selectively interfered through rapid manipulation of activity of a gene product known to play a crucial role in the regulation of synaptic plasticity. Another set of integrated analyses will be carried out to determine the possible cellular and neural mechanisms underlying the observed retrieval deficits. Finally, detailed electrophysiological analyses and additional genetic manipulations will be performed to further test the proposed hypothesis. Development and application of new genetic technology should increase researchers' ability to observe, manipulate, and discover the molecular and cellular processes underlying learning and memory in the mammalian brain. It is conceivable that such progress might eventually lead to new strategy for potential therapeutic interventions for the prevention and treatment of memory-related disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG024022-07
Application #
7118590
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Wagster, Molly V
Project Start
2000-07-15
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
7
Fiscal Year
2006
Total Cost
$478,407
Indirect Cost
Name
Boston University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Jacobs, Stephanie; Cui, Zhenzhong; Feng, Ruiben et al. (2014) Molecular and genetic determinants of the NMDA receptor for superior learning and memory functions. PLoS One 9:e111865
Jacobs, S A; Tsien, J Z (2014) Overexpression of the NR2A subunit in the forebrain impairs long-term social recognition and non-social olfactory memory. Genes Brain Behav 13:376-84
Tsien, Joe Z; Li, Meng; Osan, Remus et al. (2013) On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus. Neurobiol Learn Mem 105:200-10
Jacobs, Stephanie A; Tsien, Joe Z (2012) genetic overexpression of NR2B subunit enhances social recognition memory for different strains and species. PLoS One 7:e36387
Wang, Dong V; Tsien, Joe Z (2011) Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations. PLoS One 6:e17047
Wang, Dong V; Tsien, Joe Z (2011) Conjunctive processing of locomotor signals by the ventral tegmental area neuronal population. PLoS One 6:e16528
Li, Fei; Wang, L Phillip; Shen, Xiaoming et al. (2010) Balanced dopamine is critical for pattern completion during associative memory recall. PLoS One 5:e15401
Bibb, James A; Mayford, Mark R; Tsien, Joe Z et al. (2010) Cognition enhancement strategies. J Neurosci 30:14987-92
Kuang, Hui; Lin, Longnian; Tsien, Joe Z (2010) Temporal dynamics of distinct CA1 cell populations during unconscious state induced by ketamine. PLoS One 5:e15209
Wang, Huimin; Feng, Ruiben; Phillip Wang, L et al. (2008) CaMKII activation state underlies synaptic labile phase of LTP and short-term memory formation. Curr Biol 18:1546-54

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