Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network

Thomas J. McHugh, Matthew W. Jones, Jennifer J. Quinn, Nina Balthasar, Roberto Coppari, Joel K. Elmquist, Bradford B. Lowell, Michael S. Fanselow, Matthew A. Wilson, Susumu Tonegawa

Research output: Contribution to journalArticle

592 Scopus citations

Abstract

Forming distinct representations of multiple contexts, places, and episodes is a crucial function of the hippocampus. The dentate gyrus subregion has been suggested to fulfill this role. We have tested this hypothesis by generating and analyzing a mouse strain that lacks the gene encoding the essential subunit of the N-methyl-D-aspartate (NMDA) receptor NR1, specifically in dentate gyrus granule cells. The mutant mice performed normally in contextual fear conditioning, but were impaired in the ability to distinguish two similar contexts. A significant reduction in the context-specific modulation of firing rate was observed in the CA3 pyramidal cells when the mutant mice were transferred from one context to another. These results provide evidence that NMDA receptors in the granule cells of the dentate gyrus play a crucial role in the process of pattern separation.

Original languageEnglish (US)
Pages (from-to)94-99
Number of pages6
JournalScience
Volume317
Issue number5834
DOIs
StatePublished - Jul 6 2007

ASJC Scopus subject areas

  • General

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    McHugh, T. J., Jones, M. W., Quinn, J. J., Balthasar, N., Coppari, R., Elmquist, J. K., Lowell, B. B., Fanselow, M. S., Wilson, M. A., & Tonegawa, S. (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science, 317(5834), 94-99. https://doi.org/10.1126/science.1140263