苍白球内侧部电刺激介导多巴胺D3受体调节帕金森病异动症小鼠纹状体中型多棘神经元突触功能可塑性

左旋多巴诱导异动症（LID）是晚期帕金森病（PD）患者严重的致残性服药并发症，苍白球内侧部脑深部电刺激（GPi-DBS）是合并严重LID的PD患者最直接有效的外科手段，但其治疗机制尚不明确。本课题组前期基于LID模型鼠纹状体中型多棘神经元（MSNs）的突触可塑性异常及GPi-DBS干预进行了研究，提示GPi-DBS对LID模型鼠的行为改善、M1皮层电活动及纹状体MSNs突触可塑性异常均存在调控作用。多个研究提示多巴胺D3受体（D3R）可能参与纹状体D1型MSNs异常激活与突触功能可塑性障碍并介导LID的发生，GPi-DBS治疗LID是否通过D3R介导了类似调节机制以及如何调节，目前尚无研究。本课题拟以转基因cre-D1 C57小鼠构建LID小鼠模型，采用膜片钳、荧光成像等技术，从电生理、microRNA、分子通路等角度探讨GPi-DBS治疗可能经D3R介导的纹状体MSNs突触可塑性调节机制

Levodopa-induced dyskinesia (LID) is a serious disability complication in patients with advanced Parkinson's disease (PD). Deep brain stimulation of the internal globus pallidus (GPi-DBS) is the most direct and effective surgical method for PD patients with severe LID, but its treatment mechanism is not clear. Our previous study was based on the abnormal synaptic plasticity of medium-sized spiny neurons (MSNs) in the striatum of LID model rats and the intervention of GPi-DBS. It is suggested that GPi-DBS can regulate the behavior improvement, M1 cortical electrical activity and striatal MSNs synaptic plasticity of LID model rats. Many studies suggest that dopamine D3 receptor (D3R) may be involved in the abnormal activation of striatal D1 MSNs and synaptic plasticity disorder and mediate the occurrence of LID. Whether GPi-DBS treatment of LID through D3R mediates similar regulation mechanism and how to regulate it has not been studied. In this study, transgenic cre-D1C57 mice were used to construct LID mouse model. Patch clamp and fluorescence imaging techniques were used to explore the potential regulation mechanism of striatal MSNs synaptic plasticity mediated by GPi-DBS through D3R from the point of view of electrophysiology, microRNA, molecular pathway and so on.