Age-related changes in circadian rhythms Our current studies are directed towards elucidating how aging disrupts biological rhythms. Age-related disintegration of circadian rhythms, especially sleep-wake cycles, lowers resistance to disease and impairs memory and cognitive function. This disintegration results from functional losses in the circadian pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN). The expression of circadian rhythms depends upon the pacemaker’s ability to integrate endogenous and exogenous time Brain sectionssignals. During aging, the circadian pacemaker loses its ability to respond to serotonin, one of the neurotransmitters which normally communicates time signals. In order to elucidate the pre- and post-synaptic mechanisms causing age-related desensitization to serotonin, we are studying synaptic release of serotonin, serotonin receptors, the serotonin transporter, as well as the interaction of serotonin with neuropeptides. These studies utilize a variety of neurochemical and behavioral techniques, including receptor autoradiography, computerized image analysis, in situ hybridization, animal surgery, and monitoring of locomotor activity rhythms. This research will provide a rational basis for novel treatments of sleep disorders in the elderly population, as well as in shift-workers and jet travelers.

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