Circadian regulation of retinomotor movements: II. The role of GABA in the regulation of cone position.

Abstract

Cone photoreceptor movements in lower vertebrates are regulated by the interaction of the light-dark cycle and an endogenous circadian clock. We have suggested that melatonin and dopamine interact to regulate dark- and light-adaptive movements, respectively, and that melatonin affects cones indirectly by inhibiting dopamine release. In fact, any factor modulating dopaminergic neurons in the retina may have effects on either cone elongation or contraction. We have utilized an in vitro eyecup preparation from the African clawed frog, Xenopus laevis, to evaluate a possible role of the neurotransmitter GABA, which is thought to tonically suppress dopamine release. GABA agonists mimic the effects of darkness and induce cone elongation; the effects of GABA agonists are blocked by dopamine. Muscimol-induced cone elongation occurs at low light intensity but is inhibited by bright light in eyecups prepared from cyclic-light-maintained animals. Although neither melatonin nor muscimol stimulates cone elongation in bright light, simultaneous application of both drugs induces elongation. The GABA antagonist picrotoxin induces cone contraction which is blocked by the dopamine receptor antagonist spiroperidol, which suggests that GABA may affect cone movement in Xenopus by regulating dopamine neurons. Consistent with this, picrotoxin-induced cone contraction is Ca+2 dependent and is blocked by high Mg+2 or the Ca+2 antagonist nifedipine. Pharmacological analysis suggests that the effects of GABA may result from its action at more than one receptor subtype. Our results support the hypothesis that dopamine is part of the light signal for cone contraction and that its suppression is part of the signal for cone elongation.