The hippocampus is critical to what is termed declarative memory, our ability to consciously recall the events of our lives and to connect us with our past. It is also vulnerable to the deleterious effects of Alzheimer's dementia, stress, alcohol, stroke and other brain insults. Thus, this region of the brain continues to be a major target for gaining insights into the biological basis of memory that could lead to treatments, which could benefit people with memory disorders. The proposed research focuses on the hippocampus and to a lesser extend its interactions with the amygdala, with the goal of advancing our basic understanding of memory processes.
Our specific aims are directed at three issues.
In Aim 1 we will determine the contributions gluatamate receptors (NMDA and AMPA) in the hippocampus and amygdala make to the mnemonic and non-mnemonic functions of these regions by studying their roles in contextual fear conditioning and memory for context.
In Aim 2 we will study memory maintenance processes that may be important for stabilizing hippocampal-dependent memories. This work is based on recent findings that for several days following a learning experience the resulting memory are vulnerable to disruption. These studies will investigate the hypothesis that glutamate receptor activation is critical to memory maintenance.
In Aim 3 we focus on hippocampal dependent memories to investigate a novel hypothesis about the function of certain immediate early genes (lEGs), specifically, that one function of lEGs is to prime the memory system to facilitate the storage of subsequent events. It has two components: (a) experience at time 1 can influence the storage of a subsequent event experienced at time 2 and (b) this effect is mediated by lEGs. We propose experiments to test the implications of both components. This work will contribute to a more complete understanding of the basic mechanisms that support declarative memory and indirectly to the development of treatments to ameliorate memory disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH061316-09
Application #
7366981
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Osborn, Bettina D
Project Start
2000-05-10
Project End
2009-11-28
Budget Start
2008-03-07
Budget End
2009-11-28
Support Year
9
Fiscal Year
2008
Total Cost
$293,452
Indirect Cost
Name
University of Colorado at Boulder
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Biedenkapp, Joseph C; Rudy, Jerry W (2009) Hippocampal and extrahippocampal systems compete for control of contextual fear: role of ventral subiculum and amygdala. Learn Mem 16:38-45
Rudy, Jerry W (2009) Context representations, context functions, and the parahippocampal-hippocampal system. Learn Mem 16:573-85
Rudy, Jerry W; Matus-Amat, Patricia (2009) DHPG activation of group 1 mGluRs in BLA enhances fear conditioning. Learn Mem 16:421-5
Huber, David E; Tian, Xing; Curran, Tim et al. (2008) The dynamics of integration and separation: ERP, MEG, and neural network studies of immediate repetition effects. J Exp Psychol Hum Percept Perform 34:1389-416
Atallah, Hisham E; Rudy, Jerry W; O'Reilly, Randall C (2008) The role of the dorsal striatum and dorsal hippocampus in probabilistic and deterministic odor discrimination tasks. Learn Mem 15:294-8
Serrano, Peter; Friedman, Eugenia L; Kenney, Jana et al. (2008) PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biol 6:2698-706
Rudy, Jerry W; Sutherland, Robert J (2008) Is it systems or cellular consolidation? Time will tell. An alternative interpretation of the Morris group's recent science paper. Neurobiol Learn Mem 89:366-9
Biedenkapp, Joseph C; Rudy, Jerry W (2007) Context preexposure prevents forgetting of a contextual fear memory: implication for regional changes in brain activation patterns associated with recent and remote memory tests. Learn Mem 14:200-3
Matus-Amat, Patricia; Higgins, Emily A; Sprunger, David et al. (2007) The role of dorsal hippocampus and basolateral amygdala NMDA receptors in the acquisition and retrieval of context and contextual fear memories. Behav Neurosci 121:721-31
Bolding, Kevin; Rudy, Jerry W (2006) Place learning in the Morris water task: making the memory stick. Learn Mem 13:278-86

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