Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism.
Despite evidence showing that anticholinergic drugs are of clinical relevance in Parkinson's disease (PD), the causal role of striatal cholinergic interneurons (CINs) in PD pathophysiology remains elusive. Here, we show that optogenetic inhibition of CINs alleviates motor deficits in PD mouse models, providing direct demonstration for their implication in parkinsonian motor dysfunctions. As neural correlates, CIN inhibition in parkinsonian mice differentially impacts the excitability of striatal D1 and D2 medium spiny neurons, normalizes pathological bursting activity in the main basal ganglia output structure, and increases the functional weight of the direct striatonigral pathway in cortical information processing. By contrast, CIN inhibition in non-lesioned mice does not affect locomotor activity, equally modulates medium spiny neuron excitability, and does not modify spontaneous or cortically driven activity in the basal ganglia output, suggesting that the role of these interneurons in motor function is highly dependent on dopamine tone.
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille cedex 9, France.
Nicolas
N
Maurice
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7291, FR3C 3512, Laboratoire de Neurosciences Cognitives, 13331 Marseille cedex 3, France.
Martine
M
Liberge
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille cedex 9, France.
Florence
F
Jaouen
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7291, FR3C 3512, Laboratoire de Neurosciences Cognitives, 13331 Marseille cedex 3, France.
Samira
S
Ztaou
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille cedex 9, France.
Marwa
M
Hanini
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7291, FR3C 3512, Laboratoire de Neurosciences Cognitives, 13331 Marseille cedex 3, France.
Jeremy
J
Camon
Departments of Bioengineering and Psychiatry and Howard Hughes Medical Institute, Stanford University, Palo Alto, CA 94305, USA.
Karl
K
Deisseroth
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7291, FR3C 3512, Laboratoire de Neurosciences Cognitives, 13331 Marseille cedex 3, France.
Marianne
M
Amalric
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille cedex 9, France.
Lydia
L
Kerkerian-Le Goff
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille cedex 9, France. Electronic address: corinne.beurrier@univ-amu.fr.
Corinne
C
Beurrier
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology* / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology* / Q000502:physiology*; D004195:Disease Models, Animal; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D020734:Parkinsonian Disorders / Q000378:metabolism