Dopamine Signaling in Circadian Photoentrainment: Consequences of Desynchrony

Abstract

Circadian rhythms, or biological oscillations of approximately 24 hours, impact almost all aspects of our lives by regulating the sleep-wake cycle, hormone release, body temperature fluctuation, and timing of food consumption. The molecular machinery governing these rhythms is similar across organisms ranging from unicellular fungi to insects, rodents, and humans. Circadian entrainment, or temporal synchrony with one's environment, is essential for survival. In mammals, the central circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and mediates entrainment to environmental conditions. While the light:dark cycle is the primary environmental cue, arousal-inducing, non-photic signals such as food consumption, exercise, and social interaction are also potent synchronizers. Many of these stimuli enhance dopaminergic signaling suggesting that a cohesive circadian physiology depends on the relationship between circadian clocks and the neuronal circuits responsible for detecting salient events. Here, we review the inner workings of mammalian circadian entrainment, and describe the health consequences of circadian rhythm disruptions with an emphasis on dopamine signaling.

Keywords: Circadian disorder; Circadian rhythms; Desynchrony; Dopamine; Jet-lag; Photoentrainment; Shift-work.

Figure 1

Phase response curve of circadian rhythms to light. a. Illustration of the photic PRC in mice. By convention, phase advances are recorded as positive values and phase delays as negative. Plot of wheel running actograms representing the locomotor response of to a brief light pulse during the b., subjective day, c., early subjective night (inducing a phase delay), and d., late subjective night (inducing a phase advance). Black bars represent wheel running activity; yellow dots indicate time of light pulses in DD; dark blue lines represent an extended regression line derived by activity onsets prior to the light pulse; red lines follow actual onset of activity after the light pulse. The duration of phase shift is quantified as the horizontal difference between the two regression lines on the day after the light pulse marked by the black arrows [40].

Figure 2

Jet-lag paradigms. Representative double-plotted actograms of an a. advance and b., delay of the LD cycle by 6 hours. Black arrows indicate the day of entrainment.

Figure 3

Drd1 expression in the SCN accelerates photoentrainment. a. Schematic representation of the Cre-dependent AAV-DIO-Drd1-HA construct used to re-express Drd1 expression within the SCN. b. Diagram of bilateral stereotaxic delivery of Drd1 re-expression virus to the SCN. c. Group analysis of days to entrain following a six-hour advance in the LD cycle; F (2,62) = 19.42; P< 0.0001; One-way ANOVA with Bonferroni post hoc comparison; n= 13-26/group; ***p < 0.0001.Data are represented as mean ± SEM. Reprinted from [40] with permission from Elsevier.