Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Department of Neurology, UCSF, San Francisco, CA 94158, USA.
Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Department of Neurology, UCSF, San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA.
Neuron. 2019 Mar 20;101(6):1042-1056. doi: 10.1016/j.neuron.2019.03.004.
Parkinson's disease (PD) is a complex, multi-system neurodegenerative disorder. The second most common neurodegenerative disorder after Alzheimer's disease, it affects approximately 1% of adults over age 60. Diagnosis follows the development of one or more of the core motor features of the disease, including tremor, slowing of movement (bradykinesia), and rigidity. However, there are numerous other motor and nonmotor disease manifestations. Many PD symptoms result directly from neurodegeneration; others are driven by aberrant activity patterns in surviving neurons. This latter phenomenon, PD circuit dysfunction, is an area of intense study, as it likely underlies our ability to treat many disease symptoms in the face of (currently) irreversible neurodegeneration. This Review will discuss key clinical features of PD and their basis in neural circuit dysfunction. We will first review important disease symptoms and some of the responsible neuropathology. We will then describe the basal ganglia-thalamocortical circuit, the major locus of PD-related circuit dysfunction, and some of the models that have influenced its study. We will review PD-related changes in network activity, subdividing findings into those that touch on the rate, rhythm, or synchronization of neurons. Finally, we suggest some critical remaining questions for the field and areas for new developments.
帕金森病（PD）是一种复杂的、多系统神经退行性疾病。它是继阿尔茨海默病之后第二常见的神经退行性疾病，影响着大约 60 岁以上成年人的 1%。诊断遵循疾病的一个或多个核心运动特征的发展，包括震颤、运动缓慢（运动迟缓）和僵硬。然而，还有许多其他的运动和非运动的疾病表现。许多 PD 症状直接源于神经退行性变；其他症状则是由存活神经元的异常活动模式驱动的。这种后一种现象，即 PD 回路功能障碍，是一个研究热点，因为它可能是我们在（目前）不可逆转的神经退行性变的情况下治疗许多疾病症状的基础。这篇综述将讨论 PD 的关键临床特征及其在神经回路功能障碍中的基础。我们将首先回顾重要的疾病症状及其相关的神经病理学。然后，我们将描述基底节-丘脑皮质回路，这是与 PD 相关的回路功能障碍的主要部位，以及一些影响其研究的模型。我们将回顾与 PD 相关的网络活动变化，将发现分为涉及神经元的频率、节律或同步性的变化。最后，我们提出了该领域的一些关键遗留问题和新的发展领域。
