Optogenetic activation of parabrachial tachykinin1 neurons drives nonphotic circadian entrainment

Mammalian circadian rhythms are primarily entrained by light, but nonphotic cues can also reorganize behavioral timing through mechanisms that remain poorly understood. Nocturnal foot shocks delivered to rodents while they forage away from the safety of their nesting area have been shown to entrain circadian behavioral rhythms and shift foraging and feeding to the daytime. To identify the neural circuits underlying this nonphotic fear entrainment, we optogenetically stimulated tachykinin 1-expressing neurons in the parabrachial nucleus (Tac1PBN) during the subjective night while the animals foraged outside of their nest, which recapitulated the total activity-rest phase switch in circadian behaviors induced by foot shocks. Furthermore, selective stimulation of Tac1PBN projections to the central amygdala (CeA) produced a significant but reduced phase shift compared to direct stimulation of Tac1PBN cell bodies. When Bmal1, a core clock gene, was conditionally deleted from the CeA, mice failed to fear-entrain, implicating the CeA molecular clock as a necessary component for fear entrainment. Together, these experiments demonstrate that activation of a defined neuronal population outside of the suprachiasmatic nucleus (SCN) can reorganize circadian behavior by engaging a non-SCN circadian oscillator network that requires an intact CeA molecular clock.