Bright light is an important environmental factor that improves cognition. For example, brighter illumination facilitates math and reading skills of children, and the performance of adults in cognitive tasks. Bright light therapy also improves cognition in mild/early-stage dementia. However, a fundamental gap exists in understanding how light modulates cognition. The objective of the proposed research is to use spatial learning in rodents as a model system to study the neural mechanisms underlying the effects of light on cognition. Specifically, we will examine the neural pathways mediating the effects of light on hippocampal-dependent learning and memory, utilizing a diurnal rodent model, the unstriped Nile grass rats (Arvichantis niloticus). There are substantial differences in how light affects nocturnal and diurnal species (e.g., light induces sleep in nocturnal mammals and wakefulness in diurnal ones, like us). Therefore, the mechanisms through which light modulates cognition must be unique for each of these chronotypes. Our pilot work has found that compared to animals housed in bright light/dark (brLD, sustained sunny days), grass rats housed in dim light/dark cycle (dimLD, sustained cloudy days) show impaired spatial memory in the Morris water maze, as well as reduced hippocampal dendritic spine density and reduced expression of the neurotropic factor BDNF. These findings firmly establish the grass rat as a unique model for elucidating how light modulates hippocampal function. The proposed project will test the central hypothesis that orexinergic inputs to the hippocampus mediate the effects of light on hippocampal-dependent spatial learning. This hypothesis stems from the PI's preliminary data indicating an overall reduction in orexinergic activity in dimLD animals and from published work documenting the orexinergic modulation of hippocampal function and spatial learning. The central hypothesis will be tested by pursuing three specific aims: 1) To establish that the impaired hippocampal function of dimLD animals is due to a reduced orexinergic stimulation of the hippocampus; 2) To demonstrate that bright light restores hippocampal function by enhancing orexinergic activity; and 3) To determine the role of orexin receptor1- mediated signaling within the hippocampus in mediating the effects of light on hippocampal functions. The approach is innovative, because it utilizes a diurnal rodent model with activity patterns more similar to humans than traditional lab rodents and implements powerful techniques involving programmable minipump infusion and gene-therapy mediated gene knockdown, to test a novel hypothesis that will lead to a better understanding of how light, via the orexin system, modulates hippocampal functions in diurnal species like ours. The work is significant, because it advances our understanding on how light modulates cognition. Ultimately, such knowledge can inform the design of lighting for optimal learning and well-being, to help identify risk factors and pharmacological targets for memory deficits, and lead to novel and more effective prevention and therapeutic strategies for cognitive decline in dementia and post-stroke patients.
The proposed research is relevant to public health because a better understanding on how light via orexin modulates cognition in diurnal species has the potential to help identify risk factors and treatments for cognitive decline in dementia and post-stroke patients. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will help to reduce the burdens of human disability.
| Soler, Joel E; Robison, Alfred J; Núñez, Antonio A et al. (2018) Light modulates hippocampal function and spatial learning in a diurnal rodent species: A study using male nile grass rat (Arvicanthis niloticus). Hippocampus 28:189-200 |
| Yan, Lily; Lonstein, Joseph S; Nunez, Antonio A (2018) Light as a modulator of emotion and cognition: Lessons learned from studying a diurnal rodent. Horm Behav : |
