Our lab has that demonstrated that circadian rhythm function is not mature at weaning or at puberty. In the diurnal degu the system is not mature until 12 months of age, 7 months after the animals reach puberty. A number of the changes between 2-12 months are dependent upon gonadal hormones.

We are following up on this work by examining the function of the circadian clock just before and early during puberty in the degu. We have thus far found that the circadian system is much less responsive to light stimuli (the primary environmental agent that synchronizes rhythms) than is the case in adults.

Our lab is also in collaboration with Dr. Jill Becker (University of Michigan) and Dr. Seema Bhatnagar University of Pennsylvania examining the circadian rhythms of rats that were exposed to stress during the last trimester of gestation and then were either allowed to self-administer cocaine during the peripubertal period or not. We found that prenatal stress alters circadian function prior to and during early puberty, and some of these alterations are still apparent in adult rats at 150 days of age. We also found that cocaine exposure in juvenile rats causes very large and apparently permanent changes in circadian rhythms that we have not seen in rats that do not self-administer until adulthood.

We have followed up on this developmental angle by looking at the development of sex differences in the rat circadian function and whether they, like the slower developing degus, might be relatively insensitive to light during the pre- and peripubertal period. Our preliminary data suggest that this is the case.

These data provide our lab with a basis to collaborate with Dr. Robert Thompson from Psychiatry to examine the effect of these developmental disruptions on reproductive function of female rats. He has a transgenic strain of rats that allow very direct examination of the functioning of the GnRH neurons that control the LH surge and ovulation. The SCN (circadian central) projects to GnRH neurons and controls the timing of ovulation. Theoretically, rats disrupted by prenatal stress and/or drug exposure, should have altered function of the HPG axis, leading to disrupted reproductive function and perhaps behavior.

Working with Dr. Megan Mahoney, we have made great progress in unraveling the circadian control over reproduction in the diurnal degu. Degus have an estrous cycle that is far more similar to the human menstrual cycle than is the rat cycle.

We have demonstrated via several functional anatomy, endocrinological manipulations and a lesion experiment that although degu mating behavior is not restricted to a few hours a day (as is the case for nocturnal rodents), the LH surge and ovulation do occur in the morning (only) as is the case for at least two other diurnal species (humans and a diurnal rat). However, the SCN control of ovulation is not dependent upon the same neurotransmitter (VIP) as in the rats. We conclude this because virtually no VIP labeled neurons project to the GnRH neurons.

However, lesions of the SCN do block estrous cycles, confirming that the circadian system is required for normal function.We will continue to pursue the mechanism by which the SCN communicates with the GnRH neurons.

Last year our lab reported the exciting data demonstrating that a high attention task is capable of reversing the chronotype of a rat such that the nocturnal animal produces entirely diurnal activity pattern. NIMH funded a new grant to pursue this research in collaboration with Dr. Martin Sarter.

Our lab has completed the first series of experiments examining the sleep patterns of the degu. As expected, they sleep more at night than during the day. However, they also offer some unique features of sleep physiology compared with other rodent models. Like humans, they spend 30% of the day sleeping, although not in a consolidated block. They have longer sleep bouts than rats and they respond differently to sleep deprivation during the day and night ­ similarly to humans but different from a rat.

We are now examining whether male and female sleep are similar/different, how it is altered by jet lag treatments, and whether sleep in juvenile animals without a mature circadian system is different from that of adults.