Regulation of arrestin mRNA levels in Limulus lateral eye: Separate and combined influences of circadian efferent input and light

Most animals experience daily changes in light and darkness. The retinas of many of these animals show concomitant rhythmic changes in the levels of m RNAs that encode proteins involved in the photoresponse. These changes may be circadian and independent of light, independent of circadian clocks and regulated by light, or regulated by a circadian clock and light. We have ta ken advantage of the organization of the Limulus visual system to examine t he separate and combined effects of signals from a circadian clock and ligh t on arrestin mRNA levels in photoreceptors. The clock that regulates photo recepaors in the lateral eye of Limulus is in the brain, and signals from t he clock reach the lateral eye via activation of a well-characterized effer ent projection in the lateral optic nerve. In the experiments described, cl ock-driven efferent input to the lateral eye was eliminated by cutting the lateral optic nerve, and light input to the lateral eye was eliminated by p lacing an opaque patch over the eye. Arrestin mRNA levels were quantified r elative to 18s mRNA with a ribonuclease protection assay. We observed the f ollowing. In lateral eyes exposed to natural diurnal light and endogenous e fferent nerve activity, the level of arrestin mRNA was higher during the da y in the light than during the night in the dark. Circadian efferent nerve activity was necessary and sufficient to produce normal daily fluctuations in the level of arrestin mRNA. Light influenced arrestin mRNA levels only i n eyes with intact and active efferent projections. We conclude that arrest in mRNA levels in lateral eye photoreceptors are controlled entirely by eff erent nerve activity, and that light exerts its effects by modulating this output from the circadian clock. Light-stimulated changes in arrestin mRNA in the vertebrate retina may likewise require interactions between light-dr iven biochemical cascades and clock output.