A neural circuit for circadian regulation of arousal

An unknown aspect of behavioral state regulation is how the circadian oscil lator of the suprachiasmatic nucleus (SCN) regulates sleep and waking. In t his report, we describe the necessary elements for a circuit that provides circadian regulation of arousal. Trans-synaptic retrograde tracing revealed a prominent indirect projection from the SCN to the noradrenergic nucleus locus coeruleus (LC), a brain arousal system. Double-labeling experiments r evealed several possible links between the SCN and the LC, including the do rsomedial (DMH) and paraventricular hypothalamic nuclei (PVN), as well as m edial and ventrolateral pre-optic areas. Lesion studies confirmed that the DMH is a substantial relay in this circuit. Next, neurophysiology experimen ts revealed circadian variations in LC impulse activity. Lesions of the DMH eliminated these circadian changes in LC activity, confirming the function ality of the SCN-DMH-LC circuit. These results reveal mechanisms for regula tion of circadian and sleep-waking functions.