深部脑刺激（DBS）被广泛应用于临床帕金森病以及其他神经精神疾病的治疗，然而DBS产生治疗效果的神经生物学机制目前还不清楚。
以往的研究表明，通过向大鼠双侧纹状体背外侧部注射6羟多巴（6-OHDA）可以制造帕金森病模型，表现为大鼠执行反应时任务（RT）的能力减退。初级运动皮层（MI）、底丘脑核（STN）和黑质网状部（SNr）是位于皮层-基底节环路上的与帕金森病密切相关的脑区。近期，中科院心理研究所心理健康院重点实验室罗非研究员、王锦琰副研究员及其团队利用清醒动物神经细胞群单位放电多通道同步记录技术，在大鼠双侧MI、STN以及SNr埋置金属微电极，观察帕金森病模型大鼠在接受双侧底丘脑核DBS后其运动功能及相关神经活动的改变。结果发现，纹状体6-OHDA注射不仅严重损伤了大鼠的运动功能，并且降低了RT任务过程中对各类事件产生反应的神经元数量。双侧底丘脑核DBS能够显著改善帕金森大鼠的运动和反应能力，并且修复了与操作行为关联的皮层-基底节区域的神经活动。DBS所产生的这些行为学和电生理治疗效果可维持近1小时。因此，本研究证实了帕金森病患者行为功能损伤与皮层-基底节环路的神经元活动改变有关。更为重要的是，向底丘脑核DBS能够有效改善帕金森病引发的行为和神经活动改变。DBS效果的长时间维持提示神经可塑性机制参与了DBS对皮层-基底节环路的调节。本研究在细胞水平阐明了DBS修复帕金森病引起的运动损伤的机制，为DBS的临床应用提供了强而有力的理论依据。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of neuroscience Research, doi: 10.1002/jnr.22313.
High-frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease
Xiang-Hong Li 2, Jin-Yan Wang 1, Ge Gao 1, Jing-Yu Chang 3, Donald J. Woodward 3, Fei Luo 1 2 *
1Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
2Neuroscience Research Institute, Peking University, Beijing, China
3Neuroscience Research Institute of North Carolina, Winston-Salem, North Carolina
Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico-basal ganglia circuits.
