Role of mGluR4 in acquisition of fear learning and memory
Identifieur interne : 000F54 ( Ncbi/Merge ); précédent : 000F53; suivant : 000F55Role 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.
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DOI: 10.1016/j.neuropharm.2012.07.038
PubMed: 22884897
PubMed Central: 3508079
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Davis</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation></author><author><name sortKey="Iancu, Ovidiu D" sort="Iancu, Ovidiu D" uniqKey="Iancu O" first="Ovidiu D." last="Iancu">Ovidiu D. Iancu</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation></author><author><name sortKey="Acher, Francine" sort="Acher, Francine" uniqKey="Acher F" first="Francine" last="Acher">Francine Acher</name><affiliation wicri:level="4"><nlm:aff id="A2">Laboratoire de Chimie & Biochimie Pharmacologiques et Toxicologiques, Universite Paris Descartes, CNRS UMR 8601, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Chimie & Biochimie Pharmacologiques et Toxicologiques, Universite Paris Descartes, CNRS UMR 8601, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author><author><name sortKey="Stewart, Blair M" sort="Stewart, Blair M" uniqKey="Stewart B" first="Blair M." last="Stewart">Blair M. Stewart</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation></author><author><name sortKey="Eiwaz, Massarra A" sort="Eiwaz, Massarra A" uniqKey="Eiwaz M" first="Massarra A." last="Eiwaz">Massarra A. Eiwaz</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation></author><author><name sortKey="Duvoisin, Robert M" sort="Duvoisin, Robert M" uniqKey="Duvoisin R" first="Robert M." last="Duvoisin">Robert M. Duvoisin</name><affiliation wicri:level="4"><nlm:aff id="A3">Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation></author><author><name sortKey="Raber, Jacob" sort="Raber, Jacob" uniqKey="Raber J" first="Jacob" last="Raber">Jacob Raber</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="A4">Department of Neurology, Oregon Health & Science University, Portland, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Oregon Health & Science University, Portland, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="A5">Division of Neuroscience, ONPRC, Oregon Health & Science University, Beaverton, OR, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Neuroscience, ONPRC, Oregon Health & Science University, Beaverton, OR</wicri:regionArea><placeName><region type="state">Oregon</region><settlement type="city">Portland</settlement></placeName><orgName type="university">Université des sciences et de la médecine de l'Oregon</orgName></affiliation></author></analytic><series><title level="j">Neuropharmacology</title><idno type="ISSN">0028-3908</idno><idno type="eISSN">1873-7064</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0236217</journal-id><journal-id journal-id-type="pubmed-jr-id">6077</journal-id><journal-id journal-id-type="nlm-ta">Neuropharmacology</journal-id><journal-id journal-id-type="iso-abbrev">Neuropharmacology</journal-id><journal-title-group><journal-title>Neuropharmacology</journal-title></journal-title-group><issn pub-type="ppub">0028-3908</issn><issn pub-type="epub">1873-7064</issn></journal-meta><article-meta><article-id pub-id-type="pmid">22884897</article-id><article-id pub-id-type="pmc">3508079</article-id><article-id pub-id-type="doi">10.1016/j.neuropharm.2012.07.038</article-id><article-id pub-id-type="manuscript">NIHMS399009</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Role of mGluR4 in acquisition of fear learning and memory</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Davis</surname><given-names>Matthew J.</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Iancu</surname><given-names>Ovidiu D.</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Acher</surname><given-names>Francine</given-names></name><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Stewart</surname><given-names>Blair M.</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Eiwaz</surname><given-names>Massarra A.</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Duvoisin</surname><given-names>Robert M.</given-names></name><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Raber</surname><given-names>Jacob</given-names></name><xref ref-type="aff" rid="A1">a</xref><xref ref-type="aff" rid="A4">d</xref><xref ref-type="aff" rid="A5">e</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><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></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>6</day><month>8</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>02</day><month>8</month><year>2012</year></pub-date><pub-date pub-type="ppub"><month>3</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>3</month><year>2014</year></pub-date><volume>66</volume><fpage>365</fpage><lpage>372</lpage><permissions><copyright-statement>© 2012 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2012</copyright-year></permissions><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><kwd-group><kwd>mGluR4</kwd><kwd>fear conditioning</kwd><kwd>mice</kwd><kwd>cued</kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Institute of Mental Health : NIMH</funding-source><award-id>R01 MH077647 || MH</award-id></award-group></funding-group></article-meta></front></pmc><affiliations><list><country><li>France</li><li>États-Unis</li></country><region><li>Oregon</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Portland</li></settlement><orgName><li>Université Paris-Descartes</li><li>Université des sciences et de la médecine de l'Oregon</li></orgName></list><tree><country name="États-Unis"><region name="Oregon"><name sortKey="Davis, Matthew J" sort="Davis, Matthew J" uniqKey="Davis M" first="Matthew J." last="Davis">Matthew J. Davis</name></region><name sortKey="Duvoisin, Robert M" sort="Duvoisin, Robert M" uniqKey="Duvoisin R" first="Robert M." last="Duvoisin">Robert M. Duvoisin</name><name sortKey="Eiwaz, Massarra A" sort="Eiwaz, Massarra A" uniqKey="Eiwaz M" first="Massarra A." last="Eiwaz">Massarra A. Eiwaz</name><name sortKey="Iancu, Ovidiu D" sort="Iancu, Ovidiu D" uniqKey="Iancu O" first="Ovidiu D." last="Iancu">Ovidiu D. Iancu</name><name sortKey="Raber, Jacob" sort="Raber, Jacob" uniqKey="Raber J" first="Jacob" last="Raber">Jacob Raber</name><name sortKey="Raber, Jacob" sort="Raber, Jacob" uniqKey="Raber J" first="Jacob" last="Raber">Jacob Raber</name><name sortKey="Raber, Jacob" sort="Raber, Jacob" uniqKey="Raber J" first="Jacob" last="Raber">Jacob Raber</name><name sortKey="Stewart, Blair M" sort="Stewart, Blair M" uniqKey="Stewart B" first="Blair M." last="Stewart">Blair M. Stewart</name></country><country name="France"><region name="Île-de-France"><name sortKey="Acher, Francine" sort="Acher, Francine" uniqKey="Acher F" first="Francine" last="Acher">Francine Acher</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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