The Nucleus Reuniens as a key control point for effects of light on learning and memory

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Many aspects of cognition, including decision making learning and memory, are influenced by our daily patterns of light exposure. Such influences encompass long-term changes in brain function, involving effects of light on our internal body clock, as well as more immediate changes in performance as a result of ongoing light exposure. Our modern lifestyles (reduced exposure to natural daylight, excess nighttime light, shift work etc.) do not optimally engage such actions and can impair performance, productivity and contribute to the cognitive decline associated with ageing or neurodegenerative diseases. This proposal will define mechanisms by which light produces acute and longer-term changes in cognitive function, information that is critical if we are to optimise environments and working practices to maximise health, well-being and productivity. Our proposal builds on our exciting new preliminary data which has identified a specific brain region, the nucleus reuniens (NRe) as a key hub for clock and light-dependent effects on learning and memory. The NRe is already established as an essential relay station for communication between two brain regions critical for memory and cognition - the hippocampus and medial prefrontal cortex (mPFC). Accordingly NRe activity is essential for various aspects of memory acquisition and recall. Our new data now reveals that the NRe contains distinct groups of cells where the brain's central clock, the suprachiasmatic nucleus (SCN), drives daily activity rhythms and others that show light-dependent changes in activity via a portion of the visual thalamus (IGL/vLGN). Based on these finds, and other latest advances in the field, we here test the roles of these clock and light-dependent pathways in: 1) regulating NRe output to the hippocampus and mPFC, 2) influencing communication between (and function of) those brain regions and associated aspects of learning and memory and 3) driving long-term changes in neural and cognitive function under environmental conditions associated with memory disruption or enhancement.To this end, our proposal draws on the complimentary expertise of the project team in large scale recording activity across neural networks involved in circadian, visual and memory processing and approaches for whole animal assessments of memory acquisition and retrieval, alongside the latest neuroscience tools for selectively manipulating the activity of brain circuity. Using such approaches we will be able to specifically identify key cell populations in SCN, IGL/vLGN and NRe, define their unique properties and selectively manipulate their activity to definitively determine their roles in modulating cognitive function at the network (including both acute and long-lasting changes associated with memory) and whole animal levels. Critically, we are also uniquely placed to address a particular barrier towards translating findings from animal research to inform applications in humans. To date, studies in this area have overwhelmingly employed nocturnal rodents (mice and rats) and there remains uncertainty regarding to extent to which important aspects of clock or light-driven controls on cognitive function will be retained in diurnal species such as ourselves. We have established a powerful new day-active laboratory rodent model that is closely related to mice, Rhabdomys, allowing us to address these important unknowns, maximising the translational potential of our findings and providing much-needed insight into mechanisms underlying cognitive control and day/night preference. Collectively then this work will comprehensively define the roles of the NRe in both immediate and long-term effects of light on learning and memory, how these contribute to impacts of the environment across day and night-active mammals and provide insight into practical applications that could promote optimal cognitive function in humans and animals.