Racing and Pacing in the Reward System: A Multi-Clock Circadian Control Over Dopaminergic Signalling

Abstract

Level of motivation, responsiveness to rewards and punishment, invigoration of exploratory behaviours, and motor performance are subject to daily fluctuations that emerge from circadian rhythms in neuronal activity of the midbrain’s dopaminergic system. While endogenous circadian rhythms are weak in the ventral tegmental area and substantia nigra pars compacta, daily changes in expression of core clock genes, ion channels, neurotransmitter receptors, dopamine-synthesising enzymes, and dopamine transporters, accompanied by changes in electrical activity, are readily observed in these nuclei. These processes cause dopamine levels released in structures innervated by midbrain dopaminergic neurons (e.g., the striatum) to oscillate in a circadian fashion. Additionally, growing evidence show that the master circadian clock located in the suprachiasmatic nucleus of the hypothalamus (SCN) rhythmically influences the activity of the dopaminergic system through various intermediate targets. Thus, circadian changes in the activity of the dopaminergic system and concomitant dopamine release observed on a daily scale are likely to be generated both intrinsically and entrained by the master clock. Previous studies have shown that the information about the value and salience of stimuli perceived by the animal is encoded in the neuronal activity of brain structures innervating midbrain dopaminergic centres. Some of these structures themselves are relatively autonomous oscillators, while others exhibit a weak endogenous circadian rhythm synchronised by the SCN. Here, we place the dopaminergic system as a hub in the extensive network of extra-SCN circadian oscillators and discuss the possible consequences of its daily entrainment for animal physiology and behaviour.

Pathophysiology of cluster headache: From the trigeminovascular system to the cerebral networks

“…Clusters owing to lesions outside the hypothalamus provide evidence for this pathophysiological hypothesis, and genetic research has linked numerous genes involved in the control of the hypothalamic clock to CH, including the CLOCK, NR1D1, PER, and cryptochrome genes (1,2,117,118). The nucleus accumbens, midbrain, and substantia nigra are examples of other brain areas that express the same genes and are locations of extra-SCN clocks (119)(120)(121)(122). As with any disease model, modern working patterns and lifestyles are frequent sources of circadian misalignment, which encourages disruption of the body's internal physiological clock and lowers the threshold for bout recurrence (123).…”

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

“… 71 Circadian rhythms controlled by SCN and other brain structures (retina, CP, cortex, hippocampus, nucleus accumbens) could regulate brain fluids dynamics, CSF clearance, activity of membrane transporters, dopaminergic signaling and reward system feeding behaviors, drug metabolism. 68 , 69 , 72 CP is an additional source of melatonin production (even with non-circadian pattern) in the brain. 73 There is a hypothesis that melatonin released from CP in nigdht could affect water permeability of the BCSFB.…”

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“…Circadian patterns are seen in both DA and 5-HT activities in animals. While DA activity is higher during the active phase [ 123 ], the mRNA levels of tryptophan hydroxylase, the 5-HT rate-limiting biosynthesis enzyme, peak around the light transition [ 124 ]. The dramatic and persistent impact of photoperiod on 5-HT neurons depends on melatonin signaling [ 80 ].…”