The rhinal cortex of nonhuman primates has been identified as a crucial component of the neural network in the medial temporal lobe that subserves recognition memory. The long term goal of the proposed studies is to elucidate the neurochemical and neuroanatomical substrates of memory processes in the rhinal cortex of both rodents and nonhuman primates. Moreover, because focal drug application overcomes many of the limitations of experimental lesions, it is hoped that these investigations will further the use of focal intracerebral drug application for the analysis of the mnemonic functions of the primate temporal lobe. In particular, the role of glutamate transmission in the perirhinal cortex (PRC) of nonhuman primates will be studied in the context of object recognition memory. Recent studies by the applicant have demonstrated that blockade of glutamate receptors, specifically in the PRC of the monkey, induces a fully reversible, delay-dependent impairment of visual recognition memory as assessed by the delayed non-matching-to-sample task. These findings will be further pursued by 1) determining whether NMDA and/or AMPA KA subtypes of glutamate receptors in rhinal cortex are required for object recognition memory in the monkey, 2) comparing different a) stimulus modalities (visual vs. tactile), b) types of tasks (declarative vs. habit), and c) task demands, for susceptibility to impairment by glutamate antagonist treatments in PRC, 3) determining whether the effects of glutamate blockade in PRC depend upon the treatment being present at the time of memory encoding vs. retrieval, and 4) exploring the possibility that enhancing glutamate function in PRC can improve performance on difficult object recognition memory tasks. The proposed studies will employ focal intracerebral microinfusions of drugs stereotaxically directed at specific regions of the rhinal cortex in awake, behaving monkeys trained on object recognition memory tasks. The drugs to be used include antagonists selective for NMDA and non-NMDA subtypes of glutamate receptors as well as drugs which enhance glutamate transmission. The information to be generated will be crucial to an understanding of brain regions in which dysfunction may contribute to the cognitive impairment associated with mental retardation, Alzheimer's disease, schizophrenia, AIDS-dementia, and neurodegenerative disorders. Moreover, these studies will lay the groundwork for developing site-directed therapeutic approaches for the treatment of such dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014580-03
Application #
2732621
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Project Start
1996-09-30
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Georgetown University
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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