Department of Neurology, University of Michigan Medical School, MI, USA.
J Parkinsons Dis. 2013 Jan 1;3(3):241-54. doi: 10.3233/JPD-130204.
Incomplete understanding of the systems-level pathophysiology of Parkinson Disease (PD) remains a significant barrier to improving its treatment. Substantial progress has been made, however, due to the availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons. This review discusses the in vivo electrophysiology of basal ganglia (BG), thalamic, and cortical regions after dopamine-depleting lesions. These include firing rate changes, neuronal burst-firing, neuronal oscillations, and neuronal synchrony that result from a combination of local microanatomic changes and network-level interactions. While much is known of the clinical and electrophysiological phenomenology of dopamine loss, a critical gap in our conception of PD pathophysiology is the link between them. We discuss potential mechanisms by which these systems-level electrophysiological changes may emerge, as well as how they may relate to clinical parkinsonism. Proposals for an updated understanding of BG function are reviewed, with an emphasis on how emerging frameworks will guide future research into the pathophysiology and treatment of PD.
对帕金森病 (PD) 系统水平发病机制的不完全理解仍然是改善其治疗的重大障碍。然而，由于能够使用选择性靶向单胺能（特别是多巴胺能）神经元的神经毒素，已经取得了重大进展。这篇综述讨论了多巴胺耗竭损伤后基底神经节 (BG)、丘脑和皮质区域的体内电生理学。这些包括由于局部微观解剖变化和网络水平相互作用的结合而导致的放电率变化、神经元爆发放电、神经元振荡和神经元同步。尽管我们对多巴胺缺失的临床和电生理现象有了很多了解，但我们对 PD 发病机制的理解存在一个关键的差距，即它们之间的联系。我们讨论了这些系统水平电生理变化可能出现的潜在机制，以及它们与临床帕金森病的关系。综述了对 BG 功能的更新理解的建议，重点介绍了新兴框架将如何指导 PD 发病机制和治疗的未来研究。
