CA1-specific deletion of NMDA receptors induces abnormal renewal of a learned fear response

Silke J. Hirsch, Nanda L. Regmi, Shari G. Birnbaum, Robert W. Greene

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

CA1 hippocampal N-methyl-d-aspartate-receptors (NMDARs) are necessary for contextually related learning and memory processes. Extinction, a form of learning, has been shown to require intact hippocampal NMDAR signalling. Renewal of fear expression can occur after fear extinction training, when the extinguished fear stimulus is presented in an environmental context different from the training context and thus, renewal is dependent on contextual memory. In this study, we show that a Grin1 knock-out (loss of the essential NR1 subunit for the NMDAR) restricted to the bilateral CA1 subfield of the dorsal hippocampus does not affect acquisition of learned fear, but does attenuate extinction of a cued fear response even when presented in the extinction-training context. We propose that failure to remember the (safe) extinction context is responsible for the abnormal fear response and suggest it is a dysfunctional renewal. The results highlight the difference in outcome of extinguished fear memory resulting from a partial rather than complete loss of function of the hippocampus and suggest a potential mechanism for abnormally increased fear expression in PTSD.

Original languageEnglish (US)
Pages (from-to)1374-1379
Number of pages6
JournalHippocampus
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2015

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N-Methyl-D-Aspartate Receptors
Fear
Hippocampus
Learning
Post-Traumatic Stress Disorders
Psychological Extinction
aspartic acid receptor

Keywords

  • Conditioned fear
  • Extinction
  • Hippocampus
  • NMDA receptor
  • Renewal

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

CA1-specific deletion of NMDA receptors induces abnormal renewal of a learned fear response. / Hirsch, Silke J.; Regmi, Nanda L.; Birnbaum, Shari G.; Greene, Robert W.

In: Hippocampus, Vol. 25, No. 11, 01.11.2015, p. 1374-1379.

Research output: Contribution to journalArticle

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