Integrated neural tracing and <i>in-situ</i> barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors

作者全名："Liao, Meimei; Gao, Xinwei; Chen, Chen; Li, Qi; Guo, Qingchun; Huang, He; Zhang, Erquan; Ju, Dapeng"

作者地址："[Liao, Meimei] China Agr Univ, Coll Biol Sci, Beijing 100193, Peoples R China; [Liao, Meimei; Chen, Chen; Li, Qi; Zhang, Erquan] Natl Inst Biol Sci NIBS, Beijing 102206, Peoples R China; [Gao, Xinwei; Guo, Qingchun] Chinese Inst Brain Res, Beijing 102206, Peoples R China; [Guo, Qingchun] Capital Med Univ, Sch Biomed Engn, Beijing 100069, Peoples R China; [Huang, He; Ju, Dapeng] Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing 401336, Peoples R China; [Li, Qi; Zhang, Erquan] Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res, Beijing 102206, Peoples R China"

通信作者："Ju, DP (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing 401336, Peoples R China."

来源：SCIENCE CHINA-LIFE SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001115173500003

JCR分区：Q1

影响因子：8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：circadian rhythms; SCN; output circuit; neural tracing; barcoded GFP; in situ sequencing

摘要："The circadian clock coordinates rhythms in numerous physiological processes to maintain organismal homeostasis. Since the suprachiasmatic nucleus (SCN) is widely accepted as the circadian pacemaker, it is critical to understand the neural mechanisms by which rhythmic information is transferred from the SCN to peripheral clocks. Here, we present the first comprehensive map of SCN efferent connections and suggest a molecular logic underlying these projections. The SCN projects broadly to most major regions of the brain, rather than solely to the hypothalamus and thalamus. The efferent projections from different subtypes of SCN neurons vary in distance and intensity, and blocking synaptic transmission of these circuits affects circadian rhythms in locomotion and feeding to different extents. We also developed a barcoding system to integrate retrograde tracing with in-situ sequencing, allowing us to link circuit anatomy and spatial patterns of gene expression. Analyses using this system revealed that brain regions functioning downstream of the SCN receive input from multiple neuropeptidergic cell types within the SCN, and that individual SCN neurons generally project to a single downstream brain region. This map of SCN efferent connections provides a critical foundation for future investigations into the neural circuits underlying SCN-mediated rhythms in physiology. Further, our new barcoded tracing method provides a tool for revealing the molecular logic of neuronal circuits within heterogeneous brain regions."

基金机构："National Natural Science Foundation of China [32171157, 31971090]; Ministry of Science and Technology of the People's Republic of China [2021ZD0203400]; Kuanren Talents' Project of The Second Affiliated Hospital of Chongqing Medical University"

基金资助正文："This work was supported by the National Natural Science Foundation of China (32171157, 31971090), Ministry of Science and Technology of the People's Republic of China (2021ZD0203400) and Kuanren Talents' Project of The Second Affiliated Hospital of Chongqing Medical University. We would like to thank Dr. David O'Keefe for careful reading and English language editing."