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dc.contributor.authorCrittenden, Jill R
dc.contributor.authorZhai, Shenyu
dc.contributor.authorSauvage, Magdalena
dc.contributor.authorKitsukawa, Takashi
dc.contributor.authorBurguière, Eric
dc.contributor.authorThomsen, Morgane
dc.contributor.authorZhang, Hui
dc.contributor.authorCosta, Cinzia
dc.contributor.authorMartella, Giuseppina
dc.contributor.authorGhiglieri, Veronica
dc.contributor.authorPicconi, Barbara
dc.contributor.authorPescatore, Karen A
dc.contributor.authorUnterwald, Ellen M
dc.contributor.authorJackson, Walker S
dc.contributor.authorHousman, David E
dc.contributor.authorCaine, S Barak
dc.contributor.authorSulzer, David
dc.contributor.authorCalabresi, Paolo
dc.contributor.authorSmith, Anne C
dc.contributor.authorSurmeier, D James
dc.contributor.authorGraybiel, Ann M
dc.date.accessioned2021-11-30T19:31:08Z
dc.date.available2021-11-30T19:31:08Z
dc.date.issued2021-10
dc.identifier.urihttps://hdl.handle.net/1721.1/138259
dc.description.abstractCalDAG-GEFI (CDGI) is a protein highly enriched in the striatum, particularly in the principal spiny projection neurons (SPNs). CDGI is strongly down-regulated in two hyperkinetic conditions related to striatal dysfunction: Huntington's disease and levodopa-induced dyskinesia in Parkinson's disease. We demonstrate that genetic deletion of CDGI in mice disrupts dendritic, but not somatic, M1 muscarinic receptors (M1Rs) signaling in indirect pathway SPNs. Loss of CDGI reduced temporal integration of excitatory postsynaptic potentials at dendritic glutamatergic synapses and impaired the induction of activity-dependent long-term potentiation. CDGI deletion selectively increased psychostimulant-induced repetitive behaviors, disrupted sequence learning, and eliminated M1R blockade of cocaine self-administration. These findings place CDGI as a major, but previously unrecognized, mediator of cholinergic signaling in the striatum. The effects of CDGI deletion on the self-administration of drugs of abuse and its marked alterations in hyperkinetic extrapyramidal disorders highlight CDGI's therapeutic potential.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/j.nbd.2021.105473en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceElsevieren_US
dc.titleCalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviorsen_US
dc.typeArticleen_US
dc.identifier.citationCrittenden, Jill R, Zhai, Shenyu, Sauvage, Magdalena, Kitsukawa, Takashi, Burguière, Eric et al. 2021. "CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors." Neurobiology of Disease, 158.
dc.contributor.departmentMcGovern Institute for Brain Research at MIT
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MIT
dc.relation.journalNeurobiology of Diseaseen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2021-11-30T19:28:58Z
dspace.orderedauthorsCrittenden, JR; Zhai, S; Sauvage, M; Kitsukawa, T; Burguière, E; Thomsen, M; Zhang, H; Costa, C; Martella, G; Ghiglieri, V; Picconi, B; Pescatore, KA; Unterwald, EM; Jackson, WS; Housman, DE; Caine, SB; Sulzer, D; Calabresi, P; Smith, AC; Surmeier, DJ; Graybiel, AMen_US
dspace.date.submission2021-11-30T19:29:01Z
mit.journal.volume158en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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