Abstract
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.
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Acknowledgement
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.
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Liao, M., Gao, X., Chen, C. et al. Integrated neural tracing and in-situ barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors. Sci. China Life Sci. 67, 518–528 (2024). https://doi.org/10.1007/s11427-023-2420-7
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DOI: https://doi.org/10.1007/s11427-023-2420-7