Dim light during the scotophase facilitates extreme behavioral entrainment. The thesis analyzes dim light in two separate instances: T18 entrainment and bifurcation. In the first chapter, mice were significantly more well entrained when dim light was present for at least 3 weeks or more. In its absence, full entrainment to T18 was not obtained and there were significant differences between T18 entrained mice with at least 3 weeks of dim light than those without. Additionally, mice entrained to T18 with dim light for 3 weeks displayed Type 0 strong phase resetting when released into constant conditions without dim light, indicating a more relaxed and flexible circadian system. In Chapter 2, Per2 was shown to be unimodal and rhythmic on a 24h basis.

Infertility is becoming increasingly prevalent in our society, where one in six couples are faced with difficulties in conceiving. Fertility is tightly regulated by the hypothalamic-pituitary-gonadal axis, where the hypothalamic gonadotropin-releasing hormone (GnRH) neurons and the suprachiasmatic nucleus (SCN) are most vital. Here we identify a novel transcription factor, Ventral anterior homeobox 1 (VAX1), as a critical regulator of GnRH neuron development and SCN function. By the use of transgenic mouse models, we deleted Vax1 in GnRH neurons early in development leading to a 99% reduction in GnRH expression, resulting in delayed pubertal onset, hypogonadism, infertility in both sexes, and atypical estrous cyclicity in females. Furthermore, the deletion of Vax1 in the mature SCN significantly reduced expression of the key SCN peptide, VIP, which was associated with disrupted wheel-running activity. The weakened SCN output led to female subfertility, while the males were unaffected. These data together highlight the importance of VAX1 in both the developmental stage of fertility and its maintenance through adulthood.