The hormone melatonin is a molecule secreted by the brain on a circadian basis. Thee is evidence that it plays a role in governing sleep cycles and, in some species, reproductive readiness, but it also has been purported to influence everything from aging to cancer. It is consumed by many people, but our knowledge of what melatonin really does and where it exerts it effects is still quite incomplete. The tectum of Xenopus laevis frogs is an appropriate system in which to study melatonin's effects, since the tectum is richly endowed with melatonin receptors; in addition, visual input plays a dramatic role in the Xenopus tectum in the formation of orderly binocular projections (plasticity and preliminary data indicate that chronic melatonin prolongs the critical period during which visual input can alter axonal projections. The experiments proposed here focus on exploring the role of melatonin on tectal function in normal Xenopus and on testing further whether chronic melatonin treatment prolongs the critical period of development of binocular maps in the tectum. Levels of melatonin, melatonin receptors, and melatonin receptor mRNA will be assessed at different times of day, and under different conditions of plasticity in order to determine whether any of those parameters change in correlation with plasticity. The anatomical consequences of chronic melatonin treatment on axonal morphology will be assessed using horseradish-peroxidase filling of isthmotectal axons in order to determine where the axons' development and responses to visual input are altered by chronic melatonin. To assess whether melatonin alters neuronal transmission in the tectum, fluorescent indicators will be used to assess melatonin's effects on calcium levels in axons and cells; also patch-clamp recording from tectal cells will be used to test whether melatonin changes presynaptic transmitter release and/or postsynaptic responses to glutamate or acetylcholine. The results of these studies will provide new information on both the acute and chronic effects of melatonin in the developing and mature nervous system. These data will be relevant to our understanding of how normal patterns of melatonin secretion affect the brain and will serve to alter us to possible consequences of long-term ingestion of melatonin.
