Role of mGluR4 in acquisition of fear learning and memory
Identifieur interne : 000572 ( Pmc/Curation ); précédent : 000571; suivant : 000573Role of mGluR4 in acquisition of fear learning and memory
Auteurs : Matthew J. Davis [États-Unis] ; Ovidiu D. Iancu [États-Unis] ; Francine Acher [France] ; Blair M. Stewart [États-Unis] ; Massarra A. Eiwaz [États-Unis] ; Robert M. Duvoisin [États-Unis] ; Jacob Raber [États-Unis]Source :
- Neuropharmacology [ 0028-3908 ] ; 2012.
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 hr 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 5mg/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.
Url:
DOI: 10.1016/j.neuropharm.2012.07.038
PubMed: 22884897
PubMed Central: 3508079
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<front><div type="abstract" xml:lang="en"><p id="P1">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<sup>−/−</sup>
mice 24 hr 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<sup>−/−</sup>
and wild-type female and male mice received 10 tone-shock pairings during training. Compared to wild-type mice, mGluR4<sup>−/−</sup>
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<sup>−/−</sup>
, LSP1-2111, at 2.5 and 5mg/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<sup>−/−</sup>
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.</p>
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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0236217</journal-id>
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<contrib-group><contrib contrib-type="author"><name><surname>Davis</surname>
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<contrib contrib-type="author"><name><surname>Iancu</surname>
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<contrib contrib-type="author"><name><surname>Duvoisin</surname>
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<aff id="A1"><label>a</label>
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA</aff>
<aff id="A2"><label>b</label>
Laboratoire de Chimie & Biochimie Pharmacologiques et Toxicologiques, Universite Paris Descartes, CNRS UMR 8601, Paris, France</aff>
<aff id="A3"><label>c</label>
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA</aff>
<aff id="A4"><label>d</label>
Department of Neurology, Oregon Health & Science University, Portland, OR, USA</aff>
<aff id="A5"><label>e</label>
Division of Neuroscience, ONPRC, Oregon Health & Science University, Beaverton, OR, USA</aff>
<author-notes><corresp id="cor1"><label>*</label>
Corresponding Author: Jacob Raber, PhD, Dept of Behavioral Neuroscience, L470, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, Phone: 503-494-1424; Fax: 503-494-6877; <email>raberj@ohsu.edu</email>
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<permissions><copyright-statement>© 2012 Elsevier Ltd. All rights reserved.</copyright-statement>
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<abstract><p id="P1">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<sup>−/−</sup>
mice 24 hr 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<sup>−/−</sup>
and wild-type female and male mice received 10 tone-shock pairings during training. Compared to wild-type mice, mGluR4<sup>−/−</sup>
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<sup>−/−</sup>
, LSP1-2111, at 2.5 and 5mg/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<sup>−/−</sup>
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.</p>
</abstract>
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