Orexin (hypocretin) mediates light-dependent fluctuation of hippocampal function in a diurnal rodent.

Environmental lighting conditions play a central role in cognitive function, but the underlying mechanisms remain unclear. Utilizing a diurnal rodent model, the Nile grass rat (Arvicanthis niloticus), we previously found that daytime light intensity affects hippocampal function in this species in a manner similar to its effects in humans. Compared to animals housed in a 12:12 h bright light-dark (brLD) cycle, grass rats kept in a 12:12 h dim light-dark (dimLD) cycle showed impaired spatial memory in the Morris water maze (MWM) and reduced CA1 apical dendritic spine density. The present study explored the neural substrates mediating the effects of daylight intensity on hippocampal function focusing on the hypothalamic orexin (hypocretin) system. First, animals housed in dimLD were treated with daily intranasal administration of orexin A peptide over five training days of the MWM task. Compared to vehicle controls, this treatment led to superior spatial memory accompanied by increased phosphorylation of Ca2+ /calmodulin-dependent protein kinase II α and glutamate receptor 1 within the CA1. To assess the role of hippocampal orexinergic signaling, an adeno-associated viral vector (AAV) expressing an orexin receptor 1 (OX1R) shRNA was injected into the dorsal hippocampus targeting the CA1 of animals housed in brLD. AAV-mediated knockdown of OX1R within the hippocampus resulted in deficits in MWM performance and reduced CA1 apical dendritic spine density. These results are consistent with the view that the hypothalamic orexinergic system underlies the modulatory role of daytime illumination on hippocampal function in diurnal mammals.

Daytime Light Intensity Modulates Spatial Learning and Hippocampal Plasticity in Female Nile Grass Rats (Arvicanthis niloticus).

Light has pervasive effects on the physiology and behavior of mammals. Several human studies have shown that light modulates cognitive functions; however, the mechanisms responsible for the effects of light remain unclear. Our previous work using diurnal male Nile grass rats (Arvicanthis niloticus) revealed that reduced illuminance during the day leads to impairments in hippocampal-dependent spatial learning/memory, reduced CA1 dendritic spine density, and attenuated hippocampal brain-derived neurotrophic factor (BDNF) expression in males. The present study examined the impact of ambient light intensity on hippocampal functions in female grass rats and explored sex differences in behavioral and hippocampal responses. Female grass rats were housed in either a 12:12-hr bright light-dark (brLD, 1000 lx) or dim light-dark (dimLD, 50 lx) cycle for four weeks. The dimLD group showed impaired spatial memory in the Morris water maze task and reduced CA1 apical dendritic spine density, similar to prior observations in males. However, the behavioral deficits seen in females were more severe than those seen in males, with dimLD females showing no evidence of long-term retention over the 24-hour periods between training sessions. In contrast to the attenuated hippocampal BDNF expression found in dimLD males, there was no significant difference in the expression of BDNF and of its receptor TrkB between females in brLD and dimLD. The results suggest that, as seen in male grass rats, reduced illuminance during the day impairs hippocampal-dependent spatial memory and hippocampal plasticity in female diurnal grass rats, but the underlying signaling pathways responsible for the effects of light restriction may differ between the sexes.

Light modulates hippocampal function and spatial learning in a diurnal rodent species: A study using male nile grass rat (Arvicanthis niloticus).

The effects of light on cognitive function have been well-documented in human studies, with brighter illumination improving cognitive performance in school children, healthy adults, and patients in early stages of dementia. However, the underlying neural mechanisms are not well understood. The present study examined how ambient light affects hippocampal function using the diurnal Nile grass rats (Arvicanthis niloticus) as the animal model. Grass rats were housed in either a 12:12 h bright light-dark (brLD, 1,000 lux) or dim light-dark (dimLD, 50 lux) cycle. After 4 weeks, the dimLD group showed impaired spatial memory in the Morris Water Maze (MWM) task. The impairment in their MWM performance were reversed when the dimLD group were transferred to the brLD condition for another 4 weeks. The results suggest that lighting conditions influence cognitive function of grass rats in a way similar to that observed in humans, such that bright light is beneficial over dim light for cognitive performance. In addition to the behavioral changes, grass rats in the dimLD condition exhibited reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus, most notably in the CA1 subregion. There was also a reduction in dendritic spine density in CA1 apical dendrites in dimLD as compared to the brLD group, and the reduction was mostly in the number of mushroom and stubby spines. When dimLD animals were transferred to the brLD condition for 4 weeks, the hippocampal BDNF and dendritic spine density significantly increased. The results illustrate that not only does light intensity affect cognitive performance, but that it also impacts hippocampal structural plasticity. These studies serve as a starting point to further understand how ambient light modulates neuronal and cognitive functions in diurnal species. A mechanistic understanding of the effects of light on cognition can help to identify risk factors for cognitive decline and contribute to the development of more effective prevention and treatment of cognitive impairment in clinical populations.