The ultimate objective of the research proposed here is to examine the role of circadian (daily) rhythm disruption in the expression of human depressive disorders, using a mouse model system. Removal of the olfactory bulbs in rodents induces a syndrome of effects that closely mimic human unipolar depression. The present research is designed to investigate the hypothesis that the olfactory bulbs are a regulatory .component of the rodent circadian system, and that changes in circadian rhythms typical of patients with unipolar depression may be induced by removal of the olfactory bulbs. Period, phase and phase response curves of circadian rhythms will be compared between bulbectomized and sham-operated mice, and a complex of different rhythms will be assayed in combination with secondary lesions in the suprachiasmatic nuclei to try and identify the extent of olfactory bulb influence on three different circadian pacemakers in the rodent circadian system. The results will help describe the role of the olfactory bulbs in the regulation and expression of rodent circadian rhythms, and will be useful in developing a more complete and accurate model of human unipolar depression.
