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Originally published in Science Express on 30 May 2002
Science 12 July 2002:
Vol. 297. no. 5579, pp. 211 - 218
DOI: 10.1126/science.1071795
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Research Articles

Requirement for Hippocampal CA3 NMDA Receptors in Associative Memory Recall

Kazu Nakazawa,123 Michael C. Quirk,13* Raymond A. Chitwood,4 Masahiko Watanabe,5 Mark F. Yeckel,4dagger Linus D. Sun,13 Akira Kato,123ddagger Candice A. Carr,123 Daniel Johnston,4 Matthew A. Wilson,13 Susumu Tonegawa123§

Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which the N-methyl-D-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice. The mutant mice normally acquired and retrieved spatial reference memory in the Morris water maze, but they were impaired in retrieving this memory when presented with a fraction of the original cues. Similarly, hippocampal CA1 pyramidal cells in mutant mice displayed normal place-related activity in a full-cue environment but showed a reduction in activity upon partial cue removal. These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall.

1 Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center,
2 Howard Hughes Medical Institute, and
3 Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4 Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
5 Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
*   Present address: Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724, USA.

dagger    Present address: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA.

ddagger    Present address: Shionogi Research Laboratories, Shionogi & Co., Ltd., Koka-gun, Shiga 520-3423, Japan.

§   To whom correspondence should be addressed. E-mail: tonegawa{at}mit.edu

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