Synchronizing multiphasic circadian rhythms of rhodopsin promoter expression in rod photoreceptor cells

Abstract

SUMMARY Endogenous circadian clocks regulate day–night rhythms of animal behavior and physiology. In zebrafish, the circadian clocks are located in the pineal gland and the retina. In the retina, each photoreceptor is considered a circadian oscillator. A critical question is whether the individual circadian oscillators are synchronized. If so, the mechanism that underlies the synchronization needs to be elucidated. We generated a transgenic zebrafish line that expresses short half-life GFP under the transcriptional control of the rhodopsin promoter. Time-lapse imaging of rhodopsin promoter-driven GFP expression revealed that during 24 h in constant darkness, rhodopsin promoter expression in rod photoreceptor cells fluctuated rhythmically. However, the pattern of fluctuation differed between individual cells. In some cells, peak expression was seen in the subjective early morning, whereas in other cells,peak expression was seen in the afternoon or at night. Light transiently decreased rhodopsin expression, thereby synchronizing the multiphasic circadian oscillation. The application of dopamine or dopamine D2receptor agonist also synchronized the circadian rhythms of rhodopsin promoter expression. When the D2 receptors were pharmacologically blocked,light exposure produced no effect. This suggests that the synchronization of the circadian rhythms of rhodopsin promoter expression by light is mediated by dopamine D2 receptors. The mechanism that underlies the synchronization probably involves dopamine-mediated Ca2+ signaling pathways. Light, as well as dopamine, lowered Ca2+ influx into the rod cells, thereby resetting rhodopsin promoter expression to the initial phase.

Circadian organization of the mammalian retina: From gene regulation to physiology and diseases

“…Dopamine is required to synchronize circadian rhythms of rhodopsin promoter activity in Zebrafish rods (Yu et al, 2007), and stimulates Per2 induction and shifts the phase of the circadian clock in Xenopus photoreceptors (Cahill and Besharse, 1993; Steenhard and Besharse, 2000). Emerging experimental evidence also indicates that DA signaling plays an important role in the regulation of circadian rhythms in the mouse retina (Ruan et al, 2008; Pozdeyev et al, 2008; Jackson et al, 2011; Jackson et al, 2012).…”

Pineal Photoreceptor Cells Are Required for Maintaining the Circadian Rhythms of Behavioral Visual Sensitivity in Zebrafish

“…We generated a transgenic zebrafish line in which the pineal photoreceptor cells can be selectively ablated, thereby allowing functional studies of the effects of pineal photoreceptor cell ablation on the circadian rhythms of visual sensitivity. Taking advantage of the E. coli nitroreductase/metronidazole cell ablation system, we generated transgenic fish that express nitroreductase under the transcriptional control of cone photoreceptor cell-specific promoter Gnat2 [16], [17]. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells.…”

A design principle underlying the synchronization of oscillations in cellular systems

“…Therefore, coupling of oscillators tends to involve two negative feedback loops and one positive feedback loop (which can have either PP or NN coupling structure). There have been studies on the dynamics of coupled feedback loops (Hasty et al, 2001;Brandman et al, 2005;Locke et al, 2006;Matsu-ura et al, 2006;Kim, D. et al, 2007;Kim, J.-R. et al, 2008;Tsai et al, 2008;Shin et al, 2009) and on the synchronization of biological oscillators (Bier et al, 2000;Takamatsu et al, 2000;McMillen et al, 2002;Gonze et al, 2005;Fukuda et al, 2007;Li and Wang, 2007;Yu et al, 2007;Meng et al, 2008;Morelli et al, 2009), but these structures and their consequences have not been modeled in a general context. Kearns and colleagues (Kearns et al, 2006) show that the coupling of two positive oscillatory signals in an antiphase relationship can produce stable activity in response to stimulation, with computational simulations suggesting that the relative strength of two feedback mechanisms and their temporal relationship to each A design principle underlying the synchronization of oscillations in cellular systems Jeong-Rae Kim 1 other might account for cell-type-specific dynamic regulation.…”