Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism

Nicolas Maurice (1) , Martine Liberge (2) , Florence Jaouen (3) , Samira Ztaou (2) , Marwa Hanini , Jeremy Camon (4) , Karl Deisseroth (5) , Marianne Amalric (2) , Lydia Kerkerian-Le Goff (6) , Corinne Beurrier (6)

1 Dynamique et physiopathologie des réseaux neuronaux
2 LNC - Laboratoire de Neurosciences Cognitives [Marseille]
3 INT - Institut de Neurosciences de la Timone
4 INMED - INSERM U901 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
5 Stanford University
6 IBDM - Institut de Biologie du Développement de Marseille

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.

Domaines: Neurobiologie

Nicolas Maurice, Martine Liberge, Florence Jaouen, Samira Ztaou, Marwa Hanini, et al.. Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism. Cell Reports, 2015, 13 (4), pp.657-666. ⟨10.1016/j.celrep.2015.09.034⟩. ⟨hal-02332092⟩