Pde10a gates light responses in the SCN to regulate circadian photoentrainment

Light is the principal cue for synchronizing the circadian clock. A common feature of the clock among all organisms is the lack of responsiveness to light during the daytime. To understand the interaction between the circadian clock and light, we described the transcriptome of the suprachiasmatic nucleus (SCN) in mice across different circadian times under both constant darkness (DD) and in response to light exposure. In addition to classifying 10 distinct molecularly-defined SCN neuronal subtypes, we uncovered that SCN exhibits significant transcriptomic responsiveness to light during daytime, the so-called behavioral "dead zone". We further identified Pde10a , a cyclic nucleotide phosphodiesterase, as the first critical component for gating SCN responsiveness to light across the day and thus maintaining robust daily oscillations under regular light-dark conditions.