Instituto de Fisiología y Biofísica "Bernardo Houssay", (IFIBIO-Houssay), Grupo de Neurociencia de Sistemas, Universidad de Buenos Aires y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Eur J Neurosci. 2021 Apr;53(7):2100-2116. doi: 10.1111/ejn.14742. Epub 2020 May 2.
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.
帕金森病（PD）的特征是黑质纹状体多巴胺能神经元的退化，导致纹状体中的胆碱能过度活跃。这种胆碱能过度活跃是 PD 临床症状的原因之一。然而，这种状态的机制仍然未知。胆碱能中间神经元（ChIs）是纹状体中乙酰胆碱的主要来源。许多研究强调了它们正常生理活动的重要性，以保证正常的运动控制和目标导向行为。此外，最近使用光遗传学和化学遗传学方法的研究表明，降低 ChIs 活性可以改善帕金森病动物模型中的帕金森病症状，并改变 L-多巴诱导的运动障碍。在这里，我们回顾了描述的 ChIs 生理学改变，这些改变可能导致 PD 中的胆碱能过度活跃。最确定的发现是纹状体多巴胺能神经支配后 ChIs 内在膜兴奋性的增加。了解 PD 中 ChIs 功能障碍的分子基础可能有助于开发新的治疗工具，以恢复它们的正常活动并减少帕金森病症状，提高 PD 患者的生活质量。
