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Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network
Thomas J. McHugh,1,2*Matthew W. Jones,1*Jennifer J. Quinn,3Nina Balthasar,4Roberto Coppari,4Joel K. Elmquist,4Bradford B. Lowell,4Michael S. Fanselow,3Matthew A. Wilson,1Susumu Tonegawa1,2||
Forming distinct representations of multiple contexts, places,and episodes is a crucial function of the hippocampus. The dentategyrus subregion has been suggested to fulfill this role. Wehave tested this hypothesis by generating and analyzing a mousestrain that lacks the gene encoding the essential subunit ofthe N-methyl-D-aspartate (NMDA) receptor NR1, specifically indentate gyrus granule cells. The mutant mice performed normallyin contextual fear conditioning, but were impaired in the abilityto distinguish two similar contexts. A significant reductionin the context-specific modulation of firing rate was observedin the CA3 pyramidal cells when the mutant mice were transferredfrom one context to another. These results provide evidencethat NMDA receptors in the granule cells of the dentate gyrusplay a crucial role in the process of pattern separation.
1 The Picower Institute for Learning and Memory, RIKEN–MIT Neuroscience Research Center, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 2 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 3 Department of Psychology, University of California–Los Angeles, Los Angeles, CA 90095, USA. 4 Division of Endocrinology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
* These authors contributed equally to this work.
Present address: Department of Physiology, University of Bristol,Bristol BS8 1TD, UK.
Present address: Division of Molecular Psychiatry, Yale University,New Haven, CT 06508, USA.
Present address: Center for Hypothalamic Research, Universityof Texas Southwestern Medical Center, Dallas, TX 75390, USA.
|| To whom correspondence should be addressed. E-mail: tonegawa{at}mit.edu
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Present address: Department of Physiology, University of Bristol, Bristol BS8 1TD, UK. 
Present address: Division of Molecular Psychiatry, Yale University, New Haven, CT 06508, USA. 
Present address: Center for Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 
