Cited by 958Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

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

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McHugh, Thomas J., Jones, Matthew W., Quinn, Jennifer J., Balthasar, Nina, Coppari, Roberto, Elmquist, Joel K., Lowell, Bradford B., Fanselow, Michael S. +2 more·2007·Science

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.

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Crossref · 10.1126/science.1140263

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35 of 35 references verified0 citation errors · 0 not checkable

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  • Animals with impaired DG function are unable to differentiate between similar events or objects.

    “Behavioral studies have shown that animals with impaired DG function are unable to differentiate between similar events or objects [7], [8]”
  • Spine head size is positively correlated with mEPSC amplitude, and the functional loss of NMDA receptors in DG granule cells has been associated with impairments in pattern separation.

    “Spine head size is positively correlated with mEPSC amplitude [65], and the functional loss of NMDA receptors in DG granule cells has been associated with impairments in pattern separation [8].”
  • DA signaling within the hippocampus serves to consolidate the association of a neutral context with aversive, unconditioned stimuli by contributing to the plasticity of the CA3-CA1 circuitry that likely contributes to memory retention.

    “Thus, DA signaling within the hippocampus serves to consolidate the association of a neutral context with aversive, unconditioned stimuli by contributing to the plasticity of the CA3-CA1 circuitry that likely contributes to memory retention (McHugh et al., 2007; Rumpel et al., 2005).”

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Authors
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.
Affiliations
Beth Israel Deaconess Medical Center (US)
Corresponding author
  • McHugh, Thomas J.
  • Jones, Matthew W.
  • Quinn, Jennifer J.
  • Balthasar, Nina
  • Coppari, Roberto
  • Elmquist, Joel K.
  • Tonegawa, Susumu
Venue
Science
Published
2007-07-06
Volume
317
Issue
5834
Pages
94-99
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2092284040
Cited by
958
References
35
Citations by year
2026: 21 · 2025: 39 · 2024: 42 · 2023: 44 · 2022: 40 · 2021: 48 · 2020: 57 · 2019: 35 · 2018: 64 · 2017: 63 · 2016: 63 · 2015: 57 · 2014: 75 · 2013: 56 · 2012: 51
FWCI
24.81
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
  • Explore Bristol Research (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
National Institute of Mental Health (R01MH062122, MH62122, P50-MH58880, P50MH058880)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
dentate gyrus, NMDA receptor, NR1 subunit, pattern separation, hippocampus, granule cells, contextual fear conditioning, CA3 pyramidal cells, place learning, knockout mice
MeSH terms
Animals, Behavior, Animal, Conditioning, Psychological, Cues, Discrimination, Psychological, Fear, Hippocampus, Learning, Memory, Synaptic Transmission, Neuronal Plasticity, Recombination, Genetic, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Mice, Knockout, Maze Learning, Dentate Gyrus, Perforant Pathway, Excitatory Postsynaptic Potentials, Pattern Recognition, Physiological, Mice

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