Light and melatonin schedule neuronal differentiation in the habenular nuclei

Abstract

The formation of the embryonic brain requires the production, migration, and differentiation of neurons to be timely and coordinated. Coupling to the photoperiod could synchronize the development of neurons in the embryo. Here, we consider the effect of light and melatonin on the differentiation of embryonic neurons in zebrafish. We examine the formation of neurons in the habenular nuclei, a paired structure found near the dorsal surface of the brain adjacent to the pineal organ. Keeping embryos in constant darkness causes a temporary accumulation of habenular precursor cells, resulting in late differentiation and a long-lasting reduction in neuronal processes (neuropil). Because constant darkness delays the accumulation of the neurendocrine hormone melatonin in embryos, we looked for a link between melatonin signaling and habenular neurogenesis. A pharmacological block of melatonin receptors delays neurogenesis and reduces neuropil similarly to constant darkness, while addition of melatonin to embryos in constant darkness restores timely neurogenesis and neuropil. We conclude that light and melatonin schedule the differentiation of neurons and the formation of neural processes in the habenular nuclei.

Left-Right Asymmetry Is Required for the Habenulae to Respond to Both Visual and Olfactory Stimuli

“…To further investigate the role of sensory experience, we analyzed the visual and olfactory responses of wild-type fry and fry reared in a dark environment (Figure S5). No overt differences in functional asymmetries were observed, consistent with previous studies showing that light is not needed for establishment of asymmetric gene expression [27]. To test the contribution of olfactory input to the establishment of functional asymmetries, we compared visual responses in fish for which the olfactory pits were ablated at 1 dpf, prior to habenular innervation by mitral cells, and, again, no overt change in the asymmetry of visual responses was observed (Figure S6).…”

Asymmetry of the Brain: Development and Implications

“…Indeed, Budaev & Andrew (23) showed that eye preference for approaching or avoiding a predator depends on early exposure of embryos to light; the authors also suggested that light could influence asymmetric development of the habenulae, a pair of conserved nuclei in the forebrain of vertebrates (see Genetics of Zebrafish Epithalamus Development), rather than the visual pathway. However, absence of light was shown to delay the differentiation of habenular neurons rather than eliminate asymmetric expression of molecular markers (41). Likewise, Dreosti et al (49) failed to detect an effect of dark incubation on functional lateralization of the habenulae for visual and olfactory stimuli (see Discussion and Future Directions).…”

A review of the melatonin functions in zebrafish physiology

“…Hernandez de Borsetti et al. have hypothesized that the timing of neuronal differentiation and subsequently the appropriate outgrowth of dendrites during habenular development in zebrafish are events that require light, the presence of melatonin, and the unc119 gene, which is specifically expressed in the pineal gland .…”