Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic neurons that results in a hypercholinergic state in the striatum. This hypercholinergic state contributes to the clinical signs of PD. However, the mechanisms that underlie this state remain unknown. Cholinergic interneurons (ChIs) are the main source of acetylcholine in the striatum. Many studies have highlighted the importance of their normal physiological activity to guarantee a normal motor control and goal‐directed behaviour. Moreover, recent studies with optogenetic and chemogenetic approaches have shown that reducing ChIs activity ameliorates parkinsonian symptoms and modifies L‐dopa induced dyskinesia in PD animal models. Here, we review the described alterations in ChIs physiology that may contribute to a hypercholinergic state in PD. The best‐established finding is an increase of ChIs intrinsic membrane excitability after dopaminergic denervation of striatum. Understanding the molecular basis of ChIs dysfunction in PD could help to develop new therapeutic tools to restore their normal activity and decrease parkinsonian symptoms, improving life quality of PD patients.

中文翻译：

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帕金森氏病中的纹状体胆碱能中间神经元怎么了？关注内在的兴奋性

帕金森氏病（PD）的特征是黑质纹状体多巴胺能神经元变性，导致纹状体出现高胆碱能状态。这种高胆碱能状态有助于PD的临床体征。但是，这种状态的基础机制仍然未知。胆碱能神经元（ChIs）是纹状体中乙酰胆碱的主要来源。许多研究都强调了正常生理活动对保证正常的运动控制和目标行为的重要性。此外，最近关于光遗传学和化学遗传学方法的研究表明，降低ChIs活性可改善帕金森病症状，并改善PD动物模型中左旋多巴引起的运动障碍。在这里，我们审查在ChIs生理中描述的变化，可能会导致PD的高胆碱能状态。最好的发现是纹状体多巴胺能神经支配后ChIs固有膜兴奋性增加。了解PD中ChIs功能障碍的分子基础可以帮助开发新的治疗工具，以恢复其正常活动并减轻帕金森氏症状，从而改善PD患者的生活质量。