Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 38, Pages 16697-16702Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1008200107
Keywords
hippocampus; learning and memory; long-term potentiation; AMPA receptor endocytosis; Morris water maze
Categories
Funding
- Canadian Institutes of Health Research [M0P-38090]
- Natural Sciences and Engineering Research Council of Canada [214991, 7808]
- Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH99-TD-B-111-004]
- Heart and Stroke Foundation.
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Although NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are candidate mechanisms for long-term spatial memory, the precise contributions of LTP and LTD remain poorly understood. Here, we report that LTP and LTD in the hippocampal CA1 region of freely moving adult rats were prevented by NMDAR 2A (GluN2A) and 2B subunit (GluN2B) preferential antagonists, respectively. These results strongly suggest that NMDAR subtype preferential antagonists are appropriate tools to probe the roles of LTP and LTD in spatial memory. Using a Morris water maze task, the LTP-blocking GluN2A antagonist had no significant effect on any aspect of performance, whereas the LTD-blocking GluN2B antagonist impaired spatial memory consolidation. Moreover, similar spatial memory deficits were induced by inhibiting the expression of LTD with intrahippocampal infusion of a short peptide that specifically interferes with AMPA receptor endocytosis. Taken together, our findings support a functional requirement of hippocampal CA1 LTD in the consolidation of long-term spatial memory.
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