Pde10a gates light responses in the SCN to regulate circadian photoentrainment

Earth's rotation around its axis provides the principal cue for synchronizing the circadian clock with environmental light. A common feature of the clock is the lack of responsiveness to light during the daytime hours. To investigate the interaction between the circadian clock and light, we analyzed the transcriptomic profiles of the suprachiasmatic nucleus (SCN) in mice across different circadian times under constant darkness (DD) and in response to light exposure. We classified SCN neurons into 10 molecularly defined subtypes and described an elaborate transcriptional program both in DD and in response to light. Notably, we uncovered that the SCN exhibits significant transcriptomic responsiveness to light during daytime, the so-called behavioral “dead zone”. We further identified Pde10a, involved in cAMP signaling, as the first critical component for gating SCN responsiveness to light across the day and for maintaining robust daily oscillations under regular light-dark conditions. Overall design: Single nucleus RNA-sequencing of the mouse anterior hypothalamus following light exposure at three key time points: Circadian Time 6 (CT6, mid-day), CT14 (early night), and CT22 (late night). At each time point, animals housed in constant darkness were either exposed to 15 minutes of bright white light (L) or kept in darkness (D), and hypothalamus tissue containing the SCN was collected 45 minutes after exposure.