膝状体间小叶如何处理光信号及影响光对昼夜节律的调控

Light entrains circadian rhythms through retina, and retinal ganglion cells (RGCs) project light signal to suprachiasmatic nucleus (SCN) – the circadian pacemaker. There are two pathways between RGCs and SCN: direct projection and indirect pathway through intergeniculate leaflet(IGL). The direct pathway is proved to be necessary for synchronization between light cycle and circadian rhythms. Although RGCs project intensively to IGL and the same axon often bifurcates to IGL and SCN, the function of this indirect pathway is not yet completely known. Some evidences show that IGL is particularly important in the entrainment of circadian rhythms by simulated natural light condition, while the mechanism is not clear. We are proposing this project to try to understand better the function of IGL in photo-entrainment and the neuronal mechanisms underlying. For many years, researchers investigating the function of IGL have not been able to separate photic and non-photic input to IGL. Here we propose optogenetic methods combined with deep brain neuronal population imaging as a strategy to investigate how photic information is processed on RGCs-IGL-SCN pathway and how circadian rhythms are modulated by light through this indirect pathway.

光信号由视网膜神经节细胞编码，经神经节细胞向昼夜节律同步中心－视交叉上核(SCN)投射，这一神经信号通路构成光信号调控昼夜节律的结构基础。光信号投射到SCN有直接与间接两个通路。直接通路是光能够将生物体的昼夜节律与之同步的基础。间接通路是视网膜神经节细胞经膝状体间小叶(IGL)向SCN投射。虽然视网膜神经节细胞向IGL的投射几乎与向SCN的投射一样密集，甚至同一个神经节细胞同时投向IGL与SCN，但是光－IGL－SCN这一间接通路的作用还不十分明确。有证据显示，模拟自然光照条件的光信号对昼夜节律的调控与IGL的关系更为密切，但其作用机制不得而知。本项目从解析光－IGL－SCN这一通路的作用机制出发，利用光遗传，深部脑区成像等新的环路研究方法，克服前人无法将光－IGL－SCN这一通路独立出来的困难，试图回答光－IGL－SCN通路如何处理光信号，以及光信号通过这一通路调控昼夜节律的环路机制。

光信号由视网膜神经节细胞编码，经神经节细胞向昼夜节律同步中心－视交叉上核(SCN)投射，这一神经信号通路是光信号调控昼夜节律的结构基础。光信号投射到SCN有直接与间接两个通路。这两个通路的神经环路和功能此前并不为人们所知。本项目的主要研究内容是间接通路，即视网膜神经节细胞经膝状体间小叶(IGL)向SCN投射，对光移动昼夜节律相位的作用及其机制。我们通过遗传学精准操控IGL区神经元，已经验证了IGL参与光授时的充分必要性，并获得了IGL区神经元参与光授时的规律。同时，我们对视网膜-IGL-SCN这一间接环路也做了深入剖析。这一部分工作有望在今年或明年发表。我们第一次揭示了光调控视网膜传入SCN的突触可塑性，这一可塑性呈现昼夜差异，却与内源节律无关，这一重要发现对理解光授时的机制，利用光推动生物节律相位具有重要意义。该工作于2018年发表在Journal of Biological Rhythms。