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Stuart C. Mangel; The Circadian Clock in the Mammalian Retina Uses Dopamine and Melatonin Receptor Activation to Control Rod and Cone Input to Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5281.
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Recent work has shown that the circadian (24-h) clock in fish and rabbit retinas regulates 1) dopamine and melatonin release (Green & Besharse, 2004; Iuvone et al., 2005; Mangel & Ribelayga, 2010) and 2) rod and cone input to cone-connected horizontal cells by controlling rod-cone electrical coupling, so that cone input dominates in the day and rod input dominates at night (Wang & Mangel, 1996; Ribelayga et al., 2004, 2008; Ribelayga & Mangel, 2010). We therefore investigated whether the retinal clock uses dopamine and melatonin to regulate rabbit ganglion cell (GC) light responses.
Pigmented rabbits were entrained to a 12-h light/12-h dark cycle before each experiment. Following surgery under infrared illumination, GC responses to dim light stimuli were extracellularly recorded in the day and night from dark-adapted rabbit eyecups maintained with Ames medium. Background illumination was maintained in the low scotopic range in the day and night during electrical recording.
Following prolonged (> 1 h) darkness, light response thresholds for ON- and OFF-transient and sustained GCs were approximately 2.5 orders of magnitude lower during the night compared to the day. Dark-adapted GCs responded to light in the low scotopic range at night, but in the mesopic range in the morning. Following prolonged dark adaptation in the day and night, repetitive bright light stimulation increased light response thresholds to a level one order of magnitude greater than that of cells recorded during the day. In both the day and night, dark-adapted GC light responses exhibited a receptive field center, but not a receptive field surround. The spontaneous activity of dark-adapted GCs was lower during the night than in the day. Under dark-adapted conditions, bath application of dopamine D1 and D2 receptor antagonists during the day decreased GC light response thresholds to that observed during the night, and bath application of luzindole, a melatonin receptor antagonist, during the night, increased GC light response thresholds to that observed during the day.
These findings suggest that the circadian clock in the rabbit retina uses dopamine D1 and D2 and melatonin receptor activation to regulate GC light responses so that cone input dominates during the day and rod input dominates at night. Due to the action of the retinal clock, dark-adapted GCs receive substantial rod input at night, but minimal rod input during the morning. In addition, although the retinal clock enhances the sensitivity of dark-adapted GCs to dim light stimuli at night, it simultaneously reduces GC spontaneous activity.
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