Psychological and behavioral studies of humans and animals suggest that the juvenile years are marked by a high capacity for learning and memory. It has been long speculated that the decrease in the performance of learning and memory afterwards is a result of the decrease in synaptic plasticity in the adult brain. The long-term goals of this project are to understand the role of dynamic regulation of synaptic plasticity in memory formation, and to provide rational strategy for improving learning and memory in the adult mammalian brain. This application will test a key hypothesis that the restoration of NMDA-mediated plasticity in the adult brain to the juvenile level will lead to an improvement in learning and memory in the adult animals. A recently developed, region-specific genetic technology will be applied to produce a series of transgenic mice to examine this hypothesis. Moreover, the pure C57Bl/6 inbred mouse strain, a preferred strain for behavioral studies, will be used for the production of all transgenic mice in this project so that the potential problems related with genetic backgrounds of different strains can be avoided. The first set of experiments aims to produce transgenic mice in which the NMDA receptor activity and plasticity are enhanced in the mouse forebrain regions specifically. An integrated analysis at cellular, electrophysiological and behavioral levels will be carried out to investigate whether the enhanced NMDAmediated synaptic plasticity will result in better learning and memory in these mice. The second set of experiments is designed to further define whether the heightened NMDA plasticity in hippocampal subregion(s) is sufficient for the enhancement in those memory tasks.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH060236-01
Application #
2885201
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Farmer, Mary E
Project Start
1999-08-01
Project End
2004-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
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
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
Liu, Jun; Wei, Wei; Kuang, Hui et al. (2013) Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories. PLoS One 8:e63590
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, Lei Phillip; Li, Fei; Wang, Dong et al. (2011) NMDA receptors in dopaminergic neurons are crucial for habit learning. Neuron 72:1055-66
O?an, Remus; Chen, Guifen; Feng, Ruiben et al. (2011) Differential consolidation and pattern reverberations within episodic cell assemblies in the mouse hippocampus. PLoS One 6:e16507
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

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