Examination of zinc in the circadian system

Abstract

Zinc is a trace element that is essential for a large number of biological and biochemical processes in the body. In the nervous system zinc is packaged into synaptic vesicles by the ZnT3 transporter, and synaptic release of zinc can influence the activity of postsynaptic cells, either directly though its own cognate receptors, or indirectly by modulating activation of receptors for other neurotransmitters. Here, we explore the anatomical and functional aspects of zinc in the circadian system. Melanopsin-containing retinal ganglion cells in the mouse retina were found to colocalize ZnT3, indicating that they can release zinc at their synaptic targets. While the master circadian clock in the hamster suprachiasmatic nucleus (SCN) was found to contain, at best, sparse zincergic input, the intergeniculate leaflet (IGL) was found to have prominent zincergic input. Levels of zinc in these areas were not affected by time of day. Additionally, IGL zinc staining persisted following enucleation, indicating other prominent sources of zinc instead of, or in addition to, the retina. Neither enhancement nor chelation of free zinc at either the SCN or IGL altered circadian responses to phase-shifting light in hamsters. Finally, entrainment, free-running, and circadian responses to light were explored in mice lacking the ZnT3 gene. In every aspect explored, the ZnT3-KO mice were not significantly different from their wildtype counterparts. These findings highlight the presence of zinc in areas critical for circadian functioning but have yet to identify a role for zinc in these areas.\n\nHighlightsO_LIThe synaptic zinc transporter ZnT3 is found in melanopsin-containing retinal ganglion cells.\nC_LIO_LIWhile zinc input to the hamster SCN was found to be sparse at best, prominent zincergic staining was found throughout the IGL.\nC_LIO_LIZinc levels in the SCN and IGL did not change between the night and day.\nC_LIO_LINeither increasing nor decreasing zinc levels in either the SCN or IGL had an influence on circadian responses to light.\nC_LIO_LIMice lacking the ZnT3 transporter did not differ from wildtype mice on a wide variety of circadian measures.\nC_LI