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GAP43 Located on Corticostriatal Terminals Restrains Novelty-Induced Hyperactivity in Mice

dc.rights.licenseopenen_US
dc.contributor.authorMAROTO, Irene
dc.contributor.authorCOSTAS-INSUA, Carlos
dc.contributor.authorMONTERO-FERNÁNDEZ, Carlos
dc.contributor.authorHERMOSO-LÓPEZ, Alba
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorLEBOUC, Margaux
dc.contributor.authorBAJO-GRAÑERAS, Raquel
dc.contributor.authorÁLVARO-BLÁZQUEZ, Alicia
dc.contributor.authorBLÁZQUEZ, Cristina
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCANNICH, Astrid
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMARSICANO, Giovanni
dc.contributor.authorMARTÍN, Ricardo
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorBAUFRETON, Jérôme
dc.contributor.authorRODRÍGUEZ-CRESPO, Ignacio
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBELLOCCHIO, Luigi
dc.contributor.authorGUZMÁN, Manuel
dc.date.accessioned2024-10-15T15:48:16Z
dc.date.available2024-10-15T15:48:16Z
dc.date.issued2024-09-25
dc.identifier.issn0270-6474en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/202511
dc.description.abstractEnGrowth-associated protein of 43 kDa (GAP43) is a key cytoskeleton-associated component of the presynaptic terminal that facilitates neuroplasticity. Downregulation of GAP43 expression has been associated to various psychiatric conditions in humans and evokes hippocampus-dependent memory impairments in mice. Despite the extensive studies conducted on hippocampal GAP43 in past decades, however, very little is known about its roles in modulating the excitatory versus inhibitory balance in other brain regions. We recently generated conditional knock-out mice in which the Gap43 gene was selectively inactivated in either telencephalic glutamatergic neurons ( Gap43 fl/fl ; Nex1 Cre mice, hereafter Glu-GAP43 −/− mice) or forebrain GABAergic neurons ( Gap43 fl/fl ; Dlx5/6 Cre mice, hereafter GABA-GAP43 −/− mice). Here, we show that Glu-GAP43 −/− but not GABA-GAP43 −/− mice of either sex show a striking hyperactive phenotype when exposed to a novel environment. This behavioral alteration of Glu-GAP43 −/− mice was linked to a selective activation of dorsal-striatum neurons, as well as to an enhanced corticostriatal glutamatergic transmission and an abrogation of corticostriatal endocannabinoid-mediated long-term depression. In line with these observations, GAP43 was abundantly expressed in corticostriatal glutamatergic terminals of wild-type mice. The novelty-induced hyperactive phenotype of Glu-GAP43 −/− mice was abrogated by chemogenetically inhibiting corticostriatal afferences with a G i -coupled “designer receptor exclusively activated by designer drugs” (DREADDs), thus further supporting that novelty-induced activity is controlled by GAP43 at corticostriatal excitatory projections. Taken together, these findings show an unprecedented regulatory role of GAP43 in the corticostriatal circuitry and provide a new mouse model with a delimited neuronal-circuit alteration for studying novelty-induced hyperactivity, a phenotypic shortfall that occurs in diverse psychiatric diseases.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enGap43
dc.subject.enCannabinoid
dc.subject.enCorticostriatal circuitry
dc.subject.enGlutamatergic transmission
dc.subject.enLong-term depression
dc.subject.enMotor activity
dc.title.enGAP43 Located on Corticostriatal Terminals Restrains Novelty-Induced Hyperactivity in Mice
dc.title.alternativeJ Neuroscien_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1523/JNEUROSCI.0701-24.2024en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.identifier.pubmed39168654en_US
bordeaux.journalJournal of Neuroscienceen_US
bordeaux.pagee0701242024en_US
bordeaux.volume44en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.issue39en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionCNRS
bordeaux.teamEndocannabinoïdes et Neuroadaptationen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04727363
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccCC BYen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Neuroscience&rft.date=2024-09-25&rft.volume=44&rft.issue=39&rft.spage=e0701242024&rft.epage=e0701242024&rft.eissn=0270-6474&rft.issn=0270-6474&rft.au=MAROTO,%20Irene&COSTAS-INSUA,%20Carlos&MONTERO-FERN%C3%81NDEZ,%20Carlos&HERMOSO-L%C3%93PEZ,%20Alba&LEBOUC,%20Margaux&rft.genre=article


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