Role of mGluR4 in acquisition of fear learning and memory

Matthew J. Davis, Ovidiu Iancu, Francine C. Acher, Blair M. Stewart, Massarra A. Eiwaz, Robert Duvoisin, Jacob Raber

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Group III metabotropic glutamate receptors (mGluRs), which are generally located presynaptically, modulate synaptic transmission by regulating neurotransmitter release. Previously we showed enhanced amygdala-dependent cued fear conditioning in mGluR4-/- mice 24 h following training involving two tone-shock pairings. In this study, we assessed the effects of modulating mGluR4 signaling on acquisition and extinction of conditioned fear. mGluR4 -/- and wild-type female and male mice received 10 tone-shock pairings during training. Compared to wild-type mice, mGluR4-/- mice showed enhanced acquisition and extinction of cued fear. Next, we assessed whether acute pharmacological stimulation of mGluR4 with the specific orthosteric mGluR4 agonist LSP1-2111 also affects acquisition and extinction of cued fear. Consistent with the enhanced acquisition of cued fear in mGluR4 -/-, LSP1-2111, at 2.5 and 5 mg/kg, inhibited acquisition of cued fear conditioning in wild-type male mice. The drug's effect on extinction was less clear and only a subtle effect was seen at 5 mg/kg. Finally, analysis of microarray data of amygdala tissues from mGluR4-/- versus wild-type and from wild-type mice treated with a mGluR4 agonist versus saline revealed a significant overlap in pattern of gene expression. Together, these data support a role for mGluR4 signaling in acquisition of fear learning and memory. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.

Original languageEnglish (US)
Pages (from-to)365-372
Number of pages8
JournalNeuropharmacology
Volume66
DOIs
StatePublished - Mar 2013

Fingerprint

Fear
Learning
Metabotropic Glutamate Receptors
Amygdala
Shock
metabotropic glutamate receptor 4
Microarray Analysis
Synaptic Transmission
Neurotransmitter Agents
Pharmacology
Gene Expression
Psychological Extinction
Pharmaceutical Preparations

Keywords

  • Cued
  • Fear conditioning
  • mGluR4
  • Mice

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Role of mGluR4 in acquisition of fear learning and memory. / Davis, Matthew J.; Iancu, Ovidiu; Acher, Francine C.; Stewart, Blair M.; Eiwaz, Massarra A.; Duvoisin, Robert; Raber, Jacob.

In: Neuropharmacology, Vol. 66, 03.2013, p. 365-372.

Research output: Contribution to journalArticle

Davis, Matthew J. ; Iancu, Ovidiu ; Acher, Francine C. ; Stewart, Blair M. ; Eiwaz, Massarra A. ; Duvoisin, Robert ; Raber, Jacob. / Role of mGluR4 in acquisition of fear learning and memory. In: Neuropharmacology. 2013 ; Vol. 66. pp. 365-372.
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