Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System

Abstract

Circadian rhythms are daily rhythms that regulate many biological processes – from gene transcription to behavior – and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian (“clock”) genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas. Thus, it is likely that dopamine is essential to mechanisms that maintain proper rhythmicity of these five brain areas. This review discusses studies that showcase different dopaminergic mechanisms that may be involved with the regulation of these brain areas’ circadian rhythms. Mechanisms include how dopamine and dopamine receptor activity directly and indirectly influence clock genes and proteins, how dopamine’s interactions with gap junctions influence daily neuronal excitability, and how dopamine’s release and effects are gated by low- and high-pass filters. Because the dopamine neurons described in this review also release the inhibitory neurotransmitter GABA which influences clock protein expression in the retina, we discuss articles that explore how GABA may contribute to the actions of dopamine neurons on circadian rhythms. Finally, to understand how the loss of function of dopamine neurons could influence circadian rhythms, we review studies linking the neurodegenerative disease Parkinson’s Disease to disruptions of circadian rhythms in these five brain areas. The purpose of this review is to summarize growing evidence that dopamine is involved in regulating circadian rhythms, either directly or indirectly, in the brain areas discussed here. An appreciation of the growing evidence of dopamine’s influence on circadian rhythms may lead to new treatments including pharmacological agents directed at alleviating the various symptoms of circadian rhythm disruption.

Spiking and Membrane Properties of Rat Olfactory Bulb Dopamine Neurons

“…Because OB DA neurons are inhibitory, they may filter out the background, tonic odors. In the context of the OB, this suggests that DA neurons may act as high-pass filters to allow stronger odor signals to be processed by the main output neurons (Korshunov et al, 2017). A similar hypothesis was described for the function of calretinin PGCs, which are also single spikers (Iseppe et al, 2016).…”

“…spiker. Therefore, these single spiker neurons are most responsive to weaker stimuli, so that they may act as high-pass filters (Korshunov et al, 2017; also see section "Discussion"). Further, to analyze whether these spiking properties differ between Top and Bottom and/or Large and Small neurons, we assigned "dummy variables" to add a quantitative measure to these qualitative properties (0 = no more than one spike at any depolarizing stimulus; 1 = multiple spiking only at weaker depolarizing stimuli).…”

“…Perhaps, higher odor concentrations could inhibit DA neurons, as did the stronger depolarization stimuli (Figures 3E,F) and steeper ramps (Figures 7D-F). If these stronger odors bypass the DAergic network in the glomerulus, then these neurons may act as high-pass filters (Korshunov et al, 2017): actively inhibiting transmission of weak/ambient odors while being quiescent in the presence of stronger odors. Thus, the activity of OB DA neurons may increase odor discrimination through the D 2 receptor (Tillerson et al, 2006) by inhibiting glutamate release from its intraglomerular OSNs and M/TCs, while having more complicated, temporal effects on its interglomerular targets (Liu et al, 2013).…”

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

“…Although this circadian dopamine input signalling system to peri‐SCN/SCN neurones to regulate clock functions controlling peripheral fuel metabolism is a unique finding, it mirrors the similar circadian dopamine regulation of striatal clock gene expression . In the striatum and several other areas of the brain, circadian dopamine‐dopamine receptor interactions regulate the circadian expression of cellular clock genes that in turn modulate (i) particular functionalities of the neurone, as well as (ii) the dopamine‐dopamine receptor circadian interaction (ie, feedback) . The circadian dopamine‐dopamine receptor interactions at the peri‐SCN/SCN may well function to regulate circadian dopamine‐dopamine receptor interactions governing clock gene expression in the striatum in that the SCN has been observed to modulate striatal circadian neuronal activities .…”

Tyrosine hydroxylase down-regulation after loss of Abelson helper integration site 1 (AHI1) promotes depression via the circadian clock pathway in mice

“…Polymorphisms in many clock genes are associated with various psychiatric disorders (19)(20)(21). Circadian gene products regulate daily oscillation of monoamine neurotransmitters, either by controlling their biosynthesis or metabolism (19,20,22). Tyrosine hydroxylase (TH), a rate-limiting enzyme for DA biosynthesis, is directly repressed by circadian nuclear receptor Rev-Erbα (23,24).…”