The central pacemaker for mammalian circadian rhythms, the suprachiasmatic nucleus (SCN), receives a wide variety of neurochemical inputs, including cholinergic projections originating in the brainstem and the basal forebrain. The circadian pattern of cholinergic influence and the role of this signal in the functioning of the SCN are still being determined. Early data suggested that acetylcholine caused phase delays in wheel running behavior when applied early in the night, and phase advances when applied late in the night, similar to the response seen following light exposure. However in vitro evidence in both rats and mice indicates that when cholinergic agonists are applied directly to the SCN, either in vivo or in vitro, they cause phase advances throughout the night, with a maximal response at circadian time (CT) 18 in rats and CT 20 in mice. This proposal will attempt to further characterize the cholinergic influence on the SCN, and test the hypothesis that this cholinergic input plays a role in regulating the sleep-wake and circadian cycles of the animal.
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