Reciprocal connections between the suprachiasmatic nucleus and the midbrain raphe nuclei: A putative role in the circadian control of behavioral states

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The primary circadian pacemaker resides within the suprachiasmatic nucleus (SCN) in the hypothalamus, and controls the circadian rhythms of virtually all mammalian behaviors and physiological processes, including sleep and wakefulness. Serotonergic neurons in the midbrain dorsal (DRN) and median (MRN) raphe nuclei have been suggested to play an important role in behavioral state control. These neurons also show circadian rhythmicity in their activity, and may be an important target of the SCN circadian signal for organizing circadian sleep-wake rhythms. There are, however, no direct efferent projections from the SCN to the DRN or the MRN, suggesting that most of the SCN neuronal output may be conveyed indirectly. In this review, we first provide an overview of the anatomical evidence for the indirect neuronal pathways from the SCN to the DRN and MRN via several hypothalamic nuclei, namely, the medial preoptic area, subparaventricular zone, and dorsomedial hypothalamic nucleus. We discuss functional evidence to suggest that the SCN may influence the regulation of sleep-wake states by sending its circadian signal through these indirect pathways to the raphe nuclei. We then consider the feedback projections from the DRN and MRN to the SCN, and discuss functional evidence to suggest that these projections carry feedback information to the SCN regarding the vigilance state of the animal. We hypothesize that the reciprocal interactions between the circadian and sleep-wake regulatory systems may ensure a stable yet adaptive rhythmicity of daily sleepwake cycles.