This project will examine the hypothesis that NMDA receptor hypofunction within hippocampal regions model? central features of the cognitive symptoms of schizophrenia. Neuropsychological studies in schizophrenic? patients have identified a core deficit in episodic memory and studies on animals strongly suggest an? essential role for NMDA receptors in the hippocampus is the storage and recall of associations that underlie? our capacity for episodic memory. The proposed studies will combine our own recent development of a? novel protocol for the assessment of specific features of episodic memory in animals and a novel technique? for spatially and temporally selective NMDA receptor knockout developed in Robert Greene's laboratory. In? collaborative studies we will explore the role of NMDA receptors in specific components of the hippocampal? circuit. We expect to dissociate a critical role for NMDA receptors in area CA3 in the association of stimuli? and their context from a critical role for NMDA receptors in area CA1 in memory for sequential events. We? also expect to dissociate a critical role for CA3 and CA1 NMDA receptors in """"""""all-or-none"""""""" episodic memory? retrieval from a crucial role for NMDA receptors in the perirhinal and entorhinal cortex in recognition based? on a sense of familiarity. Finally, we expect to identify a selective role for CA3 NMDA receptors in the linking? of related memories supporting inferences from memory. These findings will provide insights about the? functional circuitry of hippocampal NMDA receptors, of strong relevance to other center projects that employ? functional imaging, molecular and cellular biology, and computational modeling.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH060450-09
Application #
7629672
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
9
Fiscal Year
2008
Total Cost
$255,431
Indirect Cost
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
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