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

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Science China(Life Sciences) 2024年第3期67卷 518-528页

作者： Meimei Liao Xinwei Gao Chen Chen Qi Li Qingchun Guo He Huang Erquan Zhang Dapeng Ju College of Biological Sciences China Agriculture UniversityBeijing 100193China National Institute of Biological Sciences(NIBS) Beijing 102206China Chinese Institute for Brain Research Beijing 102206China School of Biomedical Engineering Capital Medical UniversityBeijing 100069China Department of Anesthesiology The Second Affiliated HospitalChongqing Medical UniversityChongqing 401336China Tsinghua Institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijing 102206China

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 SCNmediated rhythms in physiology. Further, our new barcoded tracing method provides a tool for revealing the molecular logic of neuronal circuits within heterogeneous brain regions.

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

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