Role of mGluR4 in acquisition of fear learning and memory
Identifieur interne : 001070 ( Main/Exploration ); précédent : 001069; suivant : 001071Role 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
Affiliations:
- France, États-Unis
- Oregon, Île-de-France
- Paris, Portland
- Université Paris-Descartes, Université des sciences et de la médecine de l'Oregon
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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>
</div>
</front>
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