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.

视交叉上核 (SCN) 是哺乳动物的主要昼夜节律起搏器，受环境光的影响。然而，SCN 对光响应的分子基础尚不完全清楚。我们使用 RNA/染色质免疫沉淀/单核测序与昼夜行为测定来识别小鼠 SCN 细胞类型并探索它们对光的反应。我们确定了三种对 SCN 中的光有反应的肽能细胞类型：精氨酸加压素 (AVP)、血管活性肠肽 (VIP) 和胆囊收缩素 (CCK)。在每种细胞类型中，光响应亚组富含神经元 Per-Arnt-Sim (PAS) 结构域蛋白 4 (NPAS4) 靶基因的表达。此外，缺乏Npas4的小鼠在恒定条件下具有更长的昼夜节律，对光的阻尼相位响应曲线，并降低了 SCN 中光诱导的基因表达。我们的数据表明，NPAS4 是 SCN 中对光的正常转录反应所必需的，并且对于昼夜节律行为的光相移至关重要。