视网膜—腹外侧膝状体/膝状体间小叶—外侧缰核光信息传导通路在调控抑郁样行为中的作用及机制

Although light therapy is efficacious in the treatment of depression, the mechanism of action of light in the regulation of depression remains unclear. In our previous work, a retina—ventral lateral geniculate nuclei/the intergeniculate leaflet—lateral habenula pathway (retina—vLGN/IGL—LHb) has been identified in mouse: a subset of ON type retinal ganglion cells could directly innervate neurons in vLGN/IGL that in turn inhibit neurons in LHb. It is well established that LHb inhibition improves depressive-like behaviors. We hypothesize that light might be able to treat depression through retina—vLGN/IGL—LHb pathway. In this project, we will investigate the role and mechanism of retina—vLGN/IGL—LHb pathway in the regulation of depressive-like behaviors using an array of brain circuit interrogations tools, including transsynaptic virus tracing, fiber photometry, and chemogenetics. Key questions are: 1) To investigate the function of vLGN/IGL—LHb pathway in the regulation of depressive-like behaviors. 2) To determine whether light could treat depression through retina—vLGN/IGL—LHb pathway. 3) To investigate the mechanism of retina—vLGN/IGL—LHb pathway in the regulation of depressive-like behaviors. This project aims to elucidate the brain circuit through which light could treat depression, and provide the theoretical basis for the diagnosis and treatment of depression.

光疗可显著缓解抑郁症状，但光调控抑郁情绪的神经机制尚未明确。我们前期研究发现小鼠脑中存有一条视网膜—腹外侧膝状体/膝状体间小叶—外侧缰核光信息传导通路（retina—vLGN/IGL—LHb）：视网膜中部分给光兴奋型神经节细胞可直接投射至vLGN/IGL，后者又可抑制LHb内神经元的活动。研究已表明抑制LHb可降低抑郁程度。在此基础上，我们提出光可能通过retina—vLGN/IGL—LHb通路的介导来降低抑郁程度。本课题将综合应用神经环路示踪标记、光纤记录及化学遗传等技术手段研究：1）vLGN/IGL—LHb通路在调控抑郁样行为中的作用； 2）光疗能否通过retina—vLGN/IGL—LHb通路来减少抑郁样行为； 3）retina—vLGN/IGL—LHb通路调控抑郁样行为的神经机制。本课题旨在揭示光治疗抑郁的神经环路机制，并为临床抑郁的诊治提供新思路。

抑郁相关疾病严重威胁着人类健康。研究发现外界光信息可调控机体的抑郁等情绪行为，但目前光对抑郁情绪产生调控的神经机制尚不明确。本课题旨在对光疗抗抑郁作用产生的神经机制进行系统研究。本课题成果已在Neuron，Advanced Science等高水平学术期刊发表SCI论文4篇。主要成果如下：1）揭示了vLGN/IGL—LHb 通路在调控抑郁样行为中的作用；2）明确了retina—vLGN/IGL—LHb 通路在光治疗抑郁过程中所发挥的作用。3）阐明了retina—vLGN/IGL—LHb 通路对抑郁样行为产生调控的神经机制。上述成果加深了领域内对光信息调控情绪相关行为功能及机制的理解，并可为临床光疗策略的推广及应用提供重要理论依据。