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. 2017 Oct 19;8:558. doi: 10.3389/fneur.2017.00558

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Copyright © 2017 Plano, Casiraghi, García Moro, Paladino, Golombek and Chiesa.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Circadian rhythms are driven by a vast network of oscillators regulated by multiple interconnected feedback loops that, in turn, synchronize the entire organism. Here, we show a simplified system with three interconnected components: the hypothalamus, brain stem/spinal cord, and the periphery (including behavioral rhythms as feeding/fasting and activity/rest). In the hypothalamus, the suprachiasmatic nucleus (SCN) sends synchronizing signals to different hypothalamic areas such as the medial preoptic (MPO), paraventricular (PVN), dorsomedial (DMH), and the arcuate (ARC) nuclei. All these are interconnected and send feedback information to the SCN. In addition, PVN efferences connect to two main endocrine outputs: (1) a polysynaptic pathway relaying in the superior cervical ganglion (SCG) which controls the production and release of melatonin from the pineal gland via its sympathetic innervation and (2) the secretion of corticotrophin-releasing hormone, acting on the pituitary for the release of adrenocorticotropic hormone (HPA axis) and controlling adrenal glucocorticoids (corticosterone in rodents). The SCN exert a circadian control on PVN outputs for most autonomic nervous system (ANS) functions, driven at the brain stem/medulla through parasympathetic motoneurons in the vagal dorsal motor nucleus (DMV), and by sympathetic motoneurons in the intermediolateral column (IML). The nucleus tractus solitarius (NTS) acts as an integrative center for signals coming from the hypothalamus, peripheral ANS reflexes transmitted to the DMN and the IML, and feedback to the hypothalamus (not shown). Blood-borne factors like glucose, feeding/fasting regulatory hormones and, factors derived from physical exercise, can modulate circadian rhythms at peripheral organs, as well as regulate the ANS feedback to the hypothalamus.