A role for endogenous dopamine in circadian regulation of retinal cone movement

Abstract

Cone movements in the retina of the Midas cichlid ( Cichlasoma citrinellum) take place in response both to light and endogenous circadian signals. In the normal light/dark cycle (LD) cone myoids are long at night (50–55 μm), begin to contract before expected dawn, and with light onset contract to their fully contracted positions (5 μm) which are retained throughout the day. In continuous darkness (DD) cone myoids are fully elongate at night, but undergo pre-dawn contractions to partially contracted positions which they retain throughout expected day (20–25 μm). To investigate the mechanisms by which circadian signals modulate cone myoid movements in teleost retinas, we have tested the effects on circadian cone movements of optic nerve section, intraocular injection of dopamine agonists or antagonists, and intraocular injection of melatonin. We report here that both light-induced and circadian-driven cone myoid movements can occur in the absence of efferent input from higher centres: both are retained with full amplitude after optic nerve section in vivo. Intraocular injection studies suggest that circadian regulation of cone myoid movement is mediated locally within the eye by dopamine acting via a dopaminergic D 2-receptor. Cone myoid contraction can be induced at midnight in LD or DD animals by intraocular injection of dopamine or the D 2-receptor agonist LY171555. The partially contracted cones of DD animals at expected mid-day can be induced to fully contract by intraocular injection of dopamine or the D 2-receptor agonist, or to elongate by intraocular injection of the dopamine D 2-antagonist sulpiride. Furthermore, the pre-dawn cone myoid contraction observed in both LD and DD animals in response to circadian signals can be completely blocked in DD animals by intraocular injection of the D 2-antagonist sulpiride shortly before the time of expected light onset. In contrast, circadian cone myoid movements were unaffected by intraocular injection of the D 1-receptor agonist SCH23390, or the D 1-receptor antagonist SKF38393. In addition, we report that intraocularly injected melatonin had no effect on cone position when injected in the light at mid-day, in darkness at midnight or in darkness just before expected light onset at dawn. However, both melatonin and iodomelatonin induced cone myoid contraction (the light-adaptive movement) when injected in darkness at expected mid-day in DD animals. This paradoxical result is not consistent with observations from other species in which melatonin induces dark-adaptive photoreceptor responses. Our optic nerve section observations indicate that circadian cone movement does not require efferent control. Instead they suggest that circadian cone movement is regulated locally within the eye. Our results from intraocular injection of dopamine agonists and antagonists suggest that this local circadian regulation is mediated by endogenous dopamine, acting via D 2-receptors. We find no evidence for a role for melatonin in producing dark-adaptive retinomotor movements in fish retina.