NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior

Pin Xu, Stefano Berto, Ashwinikumar Kulkarni, Byeongha Jeong, Chryshanthi Joseph, Kimberly H. Cox, Michael E. Greenberg, Taekyung Kim, Genevieve Konopka, Joseph S Takahashi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3268-3282.e6
JournalNeuron
Volume109
Issue number20
DOIs
StatePublished - Oct 20 2021

Keywords

  • light simulation
  • NPAS4
  • single-nucleus RNA sequencing
  • suprachiasmatic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

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