Melanopsin retinal ganglion cells mediate light-promoted brain development.

During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.

Time of Day-Dependent Alteration of Hippocampal Rac1 Activation Regulates Contextual Fear Memory in Rats.

Fear memory in species varies according to the time of the day. Although the underlying molecular mechanisms have been extensively explored, they remain largely unknown. Here, we report that hippocampal Rac1 activity undergoes a time of day-dependent alteration both in nocturnal rats and diurnal tree shrews and that training at the lower hippocampal Rac1 activation period during the night leads to better contextual fear memory in rats. Furthermore, day and night reversion by 24 h darkness/24 h light housing inverses the external clock time of hippocampal Rac1 activation, but the better contextual fear memory still coincides with the lower Rac1 activation in rats during the night. Interestingly, exogenous melatonin treatment promotes hippocampal Rac1 activity and impairs better contextual fear memory acquired at the lower Rac1 activation period during the night, and Rac1-specific inhibitor NSC23766 compromises the effect of melatonin. These results suggest that the time of day-dependent alteration of hippocampal Rac1 activation regulates contextual fear memory in rats by forgetting.