Dysregulated mammalian estrus cycle rescued by timed activation of VIP neurons in the circadian pacemaker and late afternoon light exposure

Jet lag and shift work disrupt the menstrual cycle and decrease fertility. The circadian pacemaker, the suprachiasmatic nucleus (SCN), is known to modulate ovulation, but the mechanism is unclear. Here we explore this connection by tracking the dynamics of vasoactive intestinal peptide (VIP)-expressing neurons in the SCN in freely-behaving mice. We show that SCNVIPactivity is time-of-day- and sex-dependent, and estrous-state-dependent in late afternoon, gating downstream activation of GnRH neurons. Afternoon light, as well as specific activation of SCNVIPneurons, rescues estrous cycle regularity and egg release in animals in altered light conditions, emphasizing the role of SCNVIPneurons as a time-dependent light-responsive switch. Our results reveal the dynamic mechanism by which SCNVIPneurons mediate light responses to regulate estrous states and demonstrate light-induced fertility rescue.One Sentence SummaryModulating and recording the activity of suprachiasmatic VIP neurons in freely behaving mice reveals their regulation of fertility by mediating the response to late afternoon light.