深部腦刺激（DBS）被廣泛應用于臨床帕金森病以及其他神經(jīng)精神疾病的治療,，然而DBS產(chǎn)生治療效果的神經(jīng)生物學機制目前還不清楚,。
以往的研究表明,，通過向大鼠雙側紋狀體背外側部注射6羥多巴（6-OHDA）可以制造帕金森病模型，表現(xiàn)為大鼠執(zhí)行反應時任務（RT）的能力減退,。初級運動皮層（MI）,、底丘腦核（STN）和黑質(zhì)網(wǎng)狀部（SNr）是位于皮層-基底節(jié)環(huán)路上的與帕金森病密切相關的腦區(qū)。近期,，中科院心理研究所心理健康院重點實驗室羅非研究員,、王錦琰副研究員及其團隊利用清醒動物神經(jīng)細胞群單位放電多通道同步記錄技術，在大鼠雙側MI,、STN以及SNr埋置金屬微電極,，觀察帕金森病模型大鼠在接受雙側底丘腦核DBS后其運動功能及相關神經(jīng)活動的改變。結果發(fā)現(xiàn),，紋狀體6-OHDA注射不僅嚴重損傷了大鼠的運動功能,，并且降低了RT任務過程中對各類事件產(chǎn)生反應的神經(jīng)元數(shù)量。雙側底丘腦核DBS能夠顯著改善帕金森大鼠的運動和反應能力,，并且修復了與操作行為關聯(lián)的皮層-基底節(jié)區(qū)域的神經(jīng)活動,。DBS所產(chǎn)生的這些行為學和電生理治療效果可維持近1小時。因此,，本研究證實了帕金森病患者行為功能損傷與皮層-基底節(jié)環(huán)路的神經(jīng)元活動改變有關,。更為重要的是，向底丘腦核DBS能夠有效改善帕金森病引發(fā)的行為和神經(jīng)活動改變,。DBS效果的長時間維持提示神經(jīng)可塑性機制參與了DBS對皮層-基底節(jié)環(huán)路的調(diào)節(jié),。本研究在細胞水平闡明了DBS修復帕金森病引起的運動損傷的機制，為DBS的臨床應用提供了強而有力的理論依據(jù),。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
