The hippocampus has held a unique position in the hearts and minds of investigators interested in the neural substrates of learning and memory since the first descriptions of its importance in humans. Decades of research have led to numerous theories and few agreements with regard to its exact role in learning and memory, but some general principles do seem to be emerging. Of particular interest to this proposal is the suggestion that the hippocampus plays a central role in the processing of contextual information and more generally, in the generation of configural representations. Unfortunately, even this tenet of hippocampal function now comes with caveats attached in that more recent studies have failed to demonstrated a role for the hippocampus in several examples of configural learning. One hypothesis to account for these discrepancies is that lesioned animals are able to utilize normally sublimated, non-configural strategies to acquire information about a task. We propose that one such strategy may be the use of discrete information about a stimulus (e.g., onset/offset) that provides information about the occurrence of a cue without requiring attention to the cue over time. We hypothesize that a task will only exhibit hippocampal dependency to the extent that it requires the animal to attend to or maintain a static representation of a cue over time in order to disambiguate an experimental setting. In order to test this hypothesis we will, 1) characterize conditional discrimination of the conditioned rat eyeblink using the same conditional cue, but with three different temporal arrangements (discrete, serial compound, and tonic), 2) evaluate the contribution of the hippocampus to the acquisition of these tasks using systemic administration of cholinergic antagonists, 3) investigate the time dependency of hippocampal involvement in these tasks using ibotenate lesions of dorsal hippocampus prior to (acquisition), during )maintenance), and following extensive training (consolidation), and finally, 4) characterize pyramidal cell activity in area CA1 during the acquisition and maintenance of the hippocampal-dependent tasks. By using a single preparation (eyeblink conditioning) and a single class of learning (conditional discrimination) we hope to fully characterize (behaviorally and cellularly) when, how, and perhaps why the hippocampus becomes engaged in learning.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM008192-22
Application #
6658416
Study Section
Special Emphasis Panel (ZGM1)
Project Start
2002-09-01
Project End
2003-08-31
Budget Start
Budget End
Support Year
22
Fiscal Year
2002
Total Cost
Indirect Cost
Name
San Jose State University
Department
Type
DUNS #
City
San Jose
State
CA
Country
United States
Zip Code
95112
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