Neural Pathways Integrating Circadian Information into the Decision to Trigger Ovulation
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It has long been known that time-of-day information is required for successful initiation of the ovulation-triggering luteinizing hormone (LH) surge. This is true in rodents and evidence suggests it is true in humans too. LH release is driven by neural release of gonadotropin-releasing hormone (GnRH) from GnRH neurons in the medial preoptic area of the hypothalamus, and these neurons represent the last neuronal control point in the brain's decision to ovulate for all vertebrates. Time of day, or circadian, information is centrally regulated by the suprachiasmatic nucleus, also in the hypothalamus. How information from the SCN reaches the GnRH neurons was not known. Female rats are similar to humans in both relevant neurological structure and behavioral and physiological responses to circadian challenges. Using female rats as a model system, I provide evidence here that the suprachiasmatic nucleus times ovulation indirectly through projections from the dorsomedial (dm) SCN to the anteroventral periventricular nucleus (AVPV), wherein kisspeptin-producing neurons integrate this circadian information with estrodiol levels. I further show evidence suggesting that the AVPV is a peripheral circadian oscillator entrained by the dmSCN, and that circadian phase within the AVPV drives its receptivity to vasopressin - the primary neuropeptide transmitter released from the dmSCN. If both hormonal (estradiol) and daily cycles are in the right phase, then kisspeptin neurons stimulate GnRH neurons to trigger the LH surge. Kisspeptin is the strongest known driver of GnRH neuronal excitation, but I demonstrate that GnRH cells still exert some kisspeptin-independent control over the shape of the LH surge by integrating information coded by the ventrolateral SCN, which influences the amplitude of the LH surge in a phase-dependant manner.