Dystonia or Dyskinesia Induced by Optogenetic Stimulation of Parafascicular Nucleus of Rat

Dyskinesia is a neurological disorder characterized by involuntary movement of the body due to the abnormal function of the basal ganglia, and the basal ganglia circuit is the target of treatment of this disease. The parafascicular nucleus (PF) plays pivotal roles in controlling of the basal ganglia, but it is not well known how PF affects the development of dyskinesia. Animal models of dyskinesia currently available have not linked to clinical study of treatment of dyskinesia. The reason of this discordance is absence of proper animal model suitable for integrative aspect of dyskinesia. This study was designed to develop an animal model of dyskinesia that is reversibly controllable by stimulating the PF using optogenetics. Fourteen animals were underwent stereotactic operation injecting a virus vector “AAV2−hSyn−ChR2−mCherry” to the lateral one third of the PF. Baseline and post-stimulation behavior test was done. As results, dyskinesias were found in 7 animals. Dyskinesia scores were significant increased after light stimulation compared to baseline. In rats with dyskinesia, it was confirmed that the mCherry was expressed in the PF, while the rats without dyskinesia did not present mCherry. In conclusion, it was found that dyskinesia could be reversibly induced when the PF was stimulated using an optogenetic method.

舞蹈病是一种由基底神经节异常功能引起的神经系统疾病，其特征为身体的不自主运动。基底神经节回路是该疾病治疗的目标。副纤维层核（PF）在调控基底神经节方面发挥着至关重要的作用，但其如何影响舞蹈病的发展尚不明确。目前可用的舞蹈病动物模型尚未与舞蹈病的临床治疗研究相联系。这种不一致的原因是缺乏适合舞蹈病综合特征的适宜动物模型。本研究旨在开发一种可通过光遗传学刺激PF实现可逆控制的舞蹈病动物模型。十四只动物接受了立体定向手术，向PF的侧三分之一注入病毒载体“AAV2−hSyn−ChR2−mCherry”。进行了基线及刺激后的行为测试。结果表明，在7只动物中发现了舞蹈病。与基线相比，光刺激后舞蹈病评分显著增加。在患有舞蹈病的大鼠中，证实mCherry在PF中表达，而未患有舞蹈病的大鼠则未呈现mCherry。综上所述，发现通过光遗传学方法刺激PF可逆诱导舞蹈病。