Maurice Nicolas, Liberge Martine, Jaouen Florence, Ztaou Samira, Hanini Marwa, Camon Jeremy, Deisseroth Karl, Amalric Marianne, Kerkerian-Le Goff Lydia, Beurrier Corinne
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.
Aix-Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), UMR 7291, FR3C 3512, Laboratoire de Neurosciences Cognitives, 13331 Marseille cedex 3, France.
Cell Rep. 2015 Oct 27;13(4):657-666. doi: 10.1016/j.celrep.2015.09.034. Epub 2015 Oct 17.
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.
尽管有证据表明抗胆碱能药物在帕金森病（PD）中具有临床相关性，但纹状体胆碱能中间神经元（CINs）在PD病理生理学中的因果作用仍不清楚。在这里，我们表明，光遗传学抑制CINs可减轻PD小鼠模型中的运动缺陷，直接证明了它们与帕金森病运动功能障碍有关。作为神经关联，帕金森病小鼠中的CIN抑制对纹状体D1和D2中型多棘神经元的兴奋性有不同影响，使主要基底神经节输出结构中的病理性爆发活动正常化，并增加皮质信息处理中直接纹状体黑质通路的功能权重。相比之下，未损伤小鼠中的CIN抑制不影响运动活动，同等调节中型多棘神经元的兴奋性，并且不改变基底神经节输出中的自发或皮质驱动活动，这表明这些中间神经元在运动功能中的作用高度依赖于多巴胺张力。
