Role of mGluR4 in acquisition of fear learning and memory

Neuropharmacology. 2013 Mar;66:365-72. doi: 10.1016/j.neuropharm.2012.07.038. Epub 2012 Aug 2.

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'.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobutyrates / pharmacology
  • Amygdala / drug effects
  • Amygdala / physiology
  • Animals
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Fear / drug effects
  • Fear / physiology*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphinic Acids / pharmacology
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / physiology*

Substances

  • Aminobutyrates
  • Excitatory Amino Acid Agonists
  • LSP1 2111
  • Phosphinic Acids
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 4