Serotonin and circadian rhythms.

Abstract

All mammal behaviors and functions exhibit synchronization with environmental rhythms. This is accomplished through an internal mechanism that generates and modulates biological rhythms. The circadian timing system, responsible for this process, is formed by connected neural structures. Pathways receive and transmit environmental cues to the central oscillator, the hypothalamic suprachiasmatic nucleus, which mediates physiological and behavioral alterations. The suprachiasmatic nucleus has three major inputs: the retinohypothalamic tract (a direct projection from the retina), the geniculohypothalamic tract (an indirect photic projection originating in the intergeniculate leaflet), and a dense serotonergic plexus from the raphe nuclei. The serotonergic pathway, a source of non-photic cues to the suprachiasmatic nucleus, modulates its activity. The importance of raphe nuclei in circadian rhythms, especially in photic responses, has been demonstrated in many studies. Serotonin is the raphe neurotransmitter that triggers phase shifts, inhibits light-induced phase-shifts, and plays a role in controlling the sleep-wake cycle. All data to date have demonstrated the importance of the raphe, through serotonergic afferents, in adjusting circadian rhythms and must therefore be considered a component of the circadian timing system. The aim of this paper is to review the literature addressing the involvement of serotonin in the modulation of circadian rhythm.

Circadian regulation of membrane physiology in neural oscillators throughout the brain

“…Despite conflicting evidence of activity rhythms in the raphe nuclei, extensive work has demonstrated that release of serotonin (5‐HT) in downstream targets—including SCN, cortex, and surrounding raphe areas—varies across the 24‐hr cycle with peak 5‐HT levels found during the day (Cagampang & Inouye, ; Cagampang, Yamazaki, Otori, & Inouye, ; Quay, ); but see also Crespi & Jouvet (). Furthermore, 5‐HT has been shown to play a large role in the process of nonphotic entrainment in the SCN (for review, see Pontes et al., ). Given the importance of neuronal activity of serotonergic neurons in seasonal affective disorder (Green, Jackson, Iwamoto, Tackenberg, & McMahon, ), a better understanding of how the local midbrain clock regulates neuronal firing is needed.…”

Chronobiology Revisited in Psychiatric Disorders: From a Translational Perspective

“…Furthermore, brain serotonin synthesis and catabolism have their own circadian rhythm, closely related to the SCN. Neuronal serotonin release in the SCN is provided in the absence of photic stimulation, and serotonin levels increase in the raphe nucleus after the beginning of the dark phase [ 107 ]. Tryptophan hydroxylase (TpH), the rate-limiting enzyme in the synthesis of serotonin, is one of the regulators of circadian rhythm in the raphe nucleus.…”

Chronobiology Revisited in Psychiatric Disorders: From a Translational Perspective

“…Furthermore, brain serotonin synthesis and catabolism have their own circadian rhythm, closely related to the SCN. Neuronal serotonin release in the SCN is provided in the absence of photic stimulation, and serotonin levels increase in the raphe nucleus after the beginning of the dark phase (Pontes et al, 2010). Tryptophan hydroxylase (TpH), the ratelimiting enzyme in the synthesis of serotonin, is one of the regulators of circadian rhythm in the raphe nucleus.…”

“…Tryptophan hydroxylase (TpH), the ratelimiting enzyme in the synthesis of serotonin, is one of the regulators of circadian rhythm in the raphe nucleus. It is known that TpH peaks during the dark phase, helping the interaction between the serotoninergic system and the SCN through the increment of serotonin levels (Pontes et al, 2010). Also, serotonergic neurotransmission alterations could cause phase shifts and changes in SCN activity affecting the phosphorylation of CLOCK proteins (Zaki et al, 2018).…”