期刊
NEURON
卷 109, 期 20, 页码 3268-+出版社
CELL PRESS
DOI: 10.1016/j.neuron.2021.07.026
关键词
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资金
- NIH [NS106657, NS028829, DC014702, MH102603]
- Howard Hughes Medical Institute
- James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition [220020467]
- Chan Zuckerberg Initiative, an advised fund of the Silicon Valley Community Foundation [HCA-A-1704-01747]
The suprachiasmatic nucleus (SCN) in mammals is regulated by environmental light and shows responses to light through different peptidergic cell types. The study found that NPAS4 plays a critical role in normal transcriptional responses to light in the SCN, affecting circadian behavior and light-induced gene expression.
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light. We identified three peptidergic cell types that responded to light in the SCN: arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). In each cell type, light-responsive subgroups were enriched for expression of neuronal Per-Arnt-Sim (PAS) domain protein 4 (NPAS4) target genes. Further, mice lacking Npas4 had a longer circadian period under constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN. Our data indicate that NPAS4 is necessary for normal transcriptional responses to light in the SCN and critical for photic phase-shifting of circadian behavior.
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