Wang Pengfei, Dai Weina, Li Hongmin, Li Weijie, Wang Yang, Liu Yichang, Wang Le, Ye Fanglei, Xu Yuming
Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450015, China.
School of Basic Medical Science, North Henan Medical University, Xinxiang, 453003, China.
Neurosci Bull. 2025 Aug 25. doi: 10.1007/s12264-025-01470-9.
Cortico-thalamic projections (the hyper-direct pathway) are implicated in levodopa-induced dyskinesia (LID), a challenging complication in the advanced stages of Parkinson's disease (PD). Excessive beta and gamma activity in PD and LID has frequently been reported in recent cross-sectional studies. We aimed to investigate the temporal features of beta and gamma activity in the hyper-direct pathway during the development of PD and LID in rats, as well as the regulatory role of the dopamine receptors DI (D1Rs) and DIII (D3Rs) in these disorders. We recorded motor behavior and electrophysiological data during the development of PD and LID, and after interventions with D1R and D3R antagonists and agonists. We demonstrated exaggerated beta-band activity in the PD state and excessive gamma-band activity during on-state dyskinesia. Subsequently, process-dependent increased beta activity correlated with bradykinesia during PD modeling, while process-dependent increased gamma activity correlated with dyskinesia under the cumulative effects of levodopa during on-state dyskinesia. Finally, both D1Rs and D3Rs were found to be involved in regulating dyskinesia and gamma activity. Dynamic oscillations are closely associated with motor behavior, and mapping dynamic oscillations may be associated with optimizing deep brain stimulation parameters and developing personalized neurotherapeutic targeting. Moreover, D1Rs and D3Rs may ameliorate dyskinesia by mediating gamma oscillations.
皮质-丘脑投射（超直接通路）与左旋多巴诱导的异动症（LID）有关，LID是帕金森病（PD）晚期具有挑战性的并发症。近期的横断面研究经常报道PD和LID中存在过度的β和γ活动。我们旨在研究大鼠PD和LID发展过程中超直接通路中β和γ活动的时间特征，以及多巴胺受体D1（D1Rs）和D3（D3Rs）在这些疾病中的调节作用。我们记录了PD和LID发展过程中以及用D1R和D3R拮抗剂和激动剂干预后的运动行为和电生理数据。我们证明了在PD状态下β波段活动增强，在异动症开启状态下γ波段活动过度。随后，在PD建模过程中，过程依赖性增加的β活动与运动迟缓相关，而在异动症开启状态下，在左旋多巴的累积作用下，过程依赖性增加的γ活动与异动症相关。最后，发现D1Rs和D3Rs均参与调节异动症和γ活动。动态振荡与运动行为密切相关，绘制动态振荡图可能与优化深部脑刺激参数和开发个性化神经治疗靶点有关。此外，D1Rs和D3Rs可能通过介导γ振荡来改善异动症。
