Huang Xiaodan, Wang Shengnan, Chen Zhiqing, Qu Wenna, Song Li, Hu Zhengfang, Xi Yue, Yang Yan, Hong Weng-Hei, Lin Song, So Kwok-Fai, Li Yulong, Huang Lu, Tao Qian, Ren Chaoran
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Department of Neurology and Stroke Center, First Affiliated Hospital of Jinan University, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human Primate Research, GHM Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Department of Neurology and Stroke Center, First Affiliated Hospital of Jinan University, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-human Primate Research, GHM Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
Cell Rep. 2025 Jun 24;44(6):115865. doi: 10.1016/j.celrep.2025.115865. Epub 2025 Jun 13.
Light has a profound impact on non-visual functions, and clinical evidence suggests bright-light therapy's effectiveness in alleviating motor and non-motor symptoms of Parkinson's disease (PD). However, the neural mechanisms underlying these effects remain unclear. Here, we demonstrate that bright-light treatment alleviates PD symptoms in mice via distinct visual circuits. Specifically, bright-light signals transmitted by the ventral lateral geniculate nucleus alleviate non-motor symptoms, such as depressive-like behaviors and spatial memory deficits. Conversely, the improvement in motor symptoms with bright-light treatment depends on a separate, disynaptic visual pathway that connects the superficial layers of the superior colliculus to the substantia nigra pars compacta (SNc). Notably, in this pathway, bright-light signals enhance the bursting activity of SNc dopaminergic neurons by upregulating HCN2 expression, a mechanism essential for motor improvements. These findings provide valuable insights into the neural mechanisms by which bright-light therapy benefits PD.
光对非视觉功能有深远影响,临床证据表明强光疗法在缓解帕金森病(PD)的运动和非运动症状方面具有有效性。然而,这些效应背后的神经机制仍不清楚。在此,我们证明强光治疗通过不同的视觉回路减轻小鼠的PD症状。具体而言,腹侧外侧膝状核传递的强光信号可减轻非运动症状,如抑郁样行为和空间记忆缺陷。相反,强光治疗对运动症状的改善依赖于一条独立的双突触视觉通路,该通路将上丘表层与黑质致密部(SNc)相连。值得注意的是,在这条通路中,强光信号通过上调HCN2表达增强SNc多巴胺能神经元的爆发活动,这是运动改善所必需的机制。这些发现为强光疗法对PD有益的神经机制提供了有价值的见解。