Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract-tracing study in rat.

The suprachiasmatic nucleus (SCN) contains a master clock for most circadian rhythms in mammals, including daily sleep-wake cycles. The ventrolateral preoptic nucleus (VLPO) plays a key role in sleep generation and, as such, might be an important target of the SCN circadian signal. However, direct SCN projections to the VLPO are limited, suggesting that most of the SCN output to the VLPO might be conveyed indirectly. We examined this possibility by microinjecting selected known major targets of SCN efferents with biotinylated dextran-amine and/or cholera toxin B subunit, followed by analyses of retrograde labelling in the SCN and anterograde labelling in the VLPO. Retrograde labelling results confirmed that the medial preoptic area, subparaventricular zone, dorsomedial hypothalamic nucleus and posterior hypothalamic area all received projections from the SCN; these projections arose predominantly from the shell, as opposed to the core, of the SCN. Anterograde labelling results indicated that these same nuclei also projected to the VLPO, mainly its medial and ventral aspects. Comparison of the results of injections of similar sizes across different target groups indicated that the rostral part of the medial preoptic area and the caudal part of the dorsomedial hypothalamic nucleus were particularly noteworthy for the abundance of both SCN source neurons and efferent fibres and terminals in the VLPO. These results suggest that the SCN might provide indirect input to the VLPO via the medial preoptic area and the dorsomedial hypothalamic nucleus, and that these indirect neuronal pathways might play a major role in circadian control of sleep-wake cycles.