Development and sexual differentiation of the circadian system of <italic>Octodon degus</italic>.

Human adolescents exhibit delays in their circadian rhythms during puberty (e.g., spontaneous waking, alertness, sleep onset). The combination of later bedtimes and earlier school days contributes to daytime sleepiness. Pubertal changes in the underlying circadian pacemaker may lead to the delay in sleep onset and spontaneous waking, because the pacemaker's endogenous period influences the phase of entrained rhythms. The data presented here clarify the immediate and long-term impact of gonadal hormone exposure during adolescence on the central circadian pacemaker of a slowly-maturing, long-lived rodent, Octodon degus (degus). Gonadally-intact degus exhibited a delay in the daily onset of activity during puberty; the phase-delay did not occur in degus gonadectomized before puberty. It is unlikely that hormones mediate circadian phase during puberty by acting directly on the underlying pacemaker, because there was no corresponding change in free-running period. Several months after puberty however, free-running period became significantly shorter in males, resulting in a sex difference in period at 12-months. Males and females gonadectomized before puberty did not exhibit a sex difference in period at any age. In a subsequent experiment, exposure to estradiol (but not dihydrotestosterone) during a post-pubertal sensitive period resulted in a shortened free-running period in males that had been castrated before puberty. Exposure to estradiol during this sensitive period did not affect free-running period in female degus. Finally, the expression of estrogen receptors within the suprachiasmatic nucleus (i.e., the site of the central circadian pacemaker) increased after puberty, around the age that free-running period becomes sexually dimorphic. However, the increase in estrogen receptor expression was not sex-specific. Together, these data indicate that sexual differentiation of the underlying circadian timekeeping mechanism in degus is a sex-specific, estrogen-mediated effect that occurs during a post-pubertal sensitive period. Questions remain about how masculinization of the circadian clock mechanism is avoided in females. So far as we know, this is the only animal model of post-pubertal sexual differentiation of the central nervous system. These data may provide a framework for understanding behavioral sex differences that emerge after puberty.Ph.D.Biological SciencesNeurosciencesPhysiological psychologyPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126057/2/3224908.pd