VIP neurons in the suprachiasmatic nucleus of female mice underlie the bidirectional influence between estrus cycle and circadian rhythm
Female mice ovulate every 4-5 days at the beginning of the dark phase. The temporal specificity of this process points to a role for the circadian clock, and the suprachiasmatic nucleus (SCN), the circadian rhythm pacemaker, in ovulation. One key neuronal population in the SCN expresses vasoactive intestinal peptide (VIP); This peptide affects gonadotropin-releasing hormone (GnRH) neurons, the population that controls the release of reproductive hormones, such as luteinizing hormone (LH). Although signalling from SCNVIP to GnRH neurons has been hypothesized to control estrous cycle timing, it is not known whether SCNVIP neurons’ activity depends on estrous cycle or whether SCNVIP neurons are the source for VIP effect on GnRH neurons. Therefore, we recorded calcium-dependent fluorescence signal from SCNVIP neurons in-vivo in both male and female mice at the transitions from light to dark, during the LH surge. Data showed that SCNVIP activity is estrous cycle and time-dependent; suggesting that SCNVIP neurons are under hormonal control. The importance of SCNVIP neurons on the regulation of estrous cycles was demonstrated by manipulated the circadian rhythm; We exposed animals to six hours’ phase advance every five days and, in a second experiment, ablated SCNVIP neurons through Caspase-3, which triggers cell-autonomous apoptosis. We observed a significant decrease in estrous cycle regularity and a significant reduction in proestrus events. These results provide direct evidence for the role of SCNVIP neurons as the source of VIP peptide in the circadian regulation of ovulation and suggest that SCNVIP neuronal activity is affected by the estrous cycle.
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