title: Role of mGluR4 in acquisition of fear learning and memory.
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'.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Davis
authors.forename: Ovidiu D
authors.initials: OD
authors.lastname: Iancu
authors.forename: Francine C
authors.initials: FC
authors.lastname: Acher
authors.forename: Blair M
authors.initials: BM
authors.lastname: Stewart
authors.forename: Massarra A
authors.initials: MA
authors.lastname: Eiwaz
authors.forename: Robert M
authors.initials: RM
authors.lastname: Duvoisin
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010721:Phosphinic Acids / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000235:genetics / Q000502:physiology*
chemical_list: D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; C555637:LSP1 2111; D010721:Phosphinic Acids; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4