My laboratory studies the molecular and neural basis of endogenous daily (circadian) rhythms in mammals. We focus upon the suprachiasmatic nucleus of the hypothalamus (SCN), a master pacemaker critical not only to general activity rhythms but also to the estrous cycle, the rhythmic secretion of many hormones, and seasonal breeding. The restriction of reproduction to a particular time of year depends upon the discrimination of daylength. The circadian system accomplishes this by SCN-regulated secretion of the hormone melatonin by the pineal gland, and detection of melatonin duration using highly specific cell membrane receptors in the brain.
We analyze gene expression in the SCN by methods which include multiple label in situ hybridization and immunocytochemistry. Retinal input triggers the expression of immediate early genes, including analogs of the Drosophila period gene, per, in order to shift the phase of the circadian clock. Nightly secretion of melatonin provides another cue which may reset the clock and allow the detection of daylength by the SCN. We are characterizing specific SCN cell types which participate in generation of the circadian oscillation, its synchronization with the outside world, and communication with the rest of the brain and ultimately the entire animal.
The appropriate timing of ovulation is controlled not only by signals from the ovary, but also by the circadian clock. We find that projections of the SCN contact not only neurons which contain estrogen receptor, but also those which regulate the pituitary. Furthermore, estrogen-responsive cells reciprocate to regulate circadian rhythms through their projections to the SCN.
What seasonal changes in brain function drive fluctuations in reproduction, sexual behavior, and energy metabolism? We find that daylength regulates the incorporation of neurons born in adulthood. This effect is not attributable to changes in the secretion of gonadal hormones. Daylength and testosterone interact to regulate androgen and opiate receptor expression in hamster brain in ways which may explain seasonal changes in sexual behavior and endocrine feedback. We are discovering mechanisms by which the nervous system integrates environmental (photoperiodic) information with