Indirect projections from the suprachiasmatic nucleus to the median preoptic nucleus in rat

We recently showed, using dual tract-tracing, that the suprachiasmatic nucleus (SCN), the site of the principal circadian clock in mammals, may have indirect projections to the sleep-promoting ventrolateral preoptic nucleus (VLPO) via relays in the medial preoptic area (MPA), dorsomedial hypothalamic nucleus (DMH), and, to a lesser extent, the subparaventricular zone (SPVZ). Here, we found that the injection of the rostral MPA, the periventricular nucleus/medial SPVZ, and the caudal DMH with a mixture of anterograde and retrograde tracers resulted in dense anterograde labeling in the median preoptic nucleus (MnPO), another key sleep-promoting nucleus in the preoptic region. The retrograde labeling in the SCN was evident as previously reported. The injections in either the MPA or the DMH produced similar densities of varicose fibers between the MnPO and the VLPO, while the injections in the SPVZ yielded a greater density of varicose fibers in the MnPO than in the VLPO. These results suggest that the MPA and DMH are potential relay nuclei to mediate SCN output to the MnPO, as well as to the VLPO, for the circadian control of sleep–wake states.