NMDA receptor hypofunction in the dentate gyrus and impaired context discrimination in adult Fmr1 knockout mice

Brennan D. Eadie, Jesse Cushman, Timal S. Kannangara, Michael S. Fanselow, Brian R. Christie

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)

Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability in humans. This X-linked disorder is caused by the transcriptional repression of a single gene, Fmr1. The loss of Fmr1 transcription prevents the production of Fragile X mental retardation protein (FMRP) which in turn disrupts the expression of a variety of key synaptic proteins that appear to be important for intellectual ability. A clear link between synaptic dysfunction and behavioral impairment has been elusive, despite the fact that several animal models of FXS have been generated. Here we report that Fmr1 knockout mice exhibit impaired bidirectional synaptic plasticity in the dentate gyrus (DG) of the hippocampus. These deficits are associated with a novel decrease in functional NMDARs (N-methyl-D-aspartate receptors). In addition, mice lacking the Fmr1 gene show impaired performance in a context discrimination task that normally requires functional NMDARs in the DG. These data indicate that Fmr1 deletion results in significant NMDAR-dependent electrophysiological and behavioral impairments specific to the DG.

Original languageEnglish
Pages (from-to)241-254
Number of pages14
JournalHippocampus
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

ASJC Scopus Subject Areas

  • Cognitive Neuroscience

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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