Cholinergic interneuron inhibition potentiates corticostriatal transmission in direct medium spiny neurons and rescues motor learning in parkinsonism.

Autor:	Laverne G; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France., Pesce J; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France., Reynders A; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France., Combrisson E; Aix Marseille University, CNRS, Institut de Neurosciences de la Timone (INT), 13005 Marseille, France., Gascon E; Aix Marseille University, CNRS, Institut de Neurosciences de la Timone (INT), 13005 Marseille, France., Melon C; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France., Kerkerian-Le Goff L; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France., Maurice N; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France., Beurrier C; Aix Marseille University, CNRS, Institut de Biologie du Développement (IBDM), 13009 Marseille, France. Electronic address: corinne.beurrier@univ-amu.fr.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Jul 05; Vol. 40 (1), pp. 111034.
DOI:	10.1016/j.celrep.2022.111034
Abstrakt:	Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson's disease. How this signal regulates the striatal network remains an open question. Here, we examine the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium spiny neurons expressing dopamine D1 receptor (D1 MSNs). Brief interruption of CIN activity has no effect in control conditions, whereas it increases glutamatergic responses in D1 MSNs after dopamine denervation. This potentiation depends upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by optogenetics/chemogenetics in vivo partially rescues long-term potentiation in MSNs and motor learning deficits in parkinsonian mice. Our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs. Competing Interests: Declaration of interests The authors declare no competing financial interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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