A ROLE FOR THE AMPAR SUBUNIT GLUA3 IN SLEEP AND MEMORY

Sleep is a fundamental process for memory consolidation. Memory formation heavily relies on the plasticity of synaptic AMPA receptors (AMPAR), which undergo sleep-related regulation. Impairment of sleep-related neural plasticity could potentially hinder memory consolidation and processing. The AMPAR subunit GluA3 has been previously implicated into mediating slow wave activity during sleep. Here, we investigate how the GluA3 AMPAR subunit influences sleep and memory. Using global GluA3 knockout (GluA3 KO ) mice, localized knockout models, the object location memory task and immediate-post learning 6-hour sleep deprivation (SD), we evaluated the role of GluA3 in spatial memory consolidation and sleep. GluA3 KO mice exhibited preserved short-term memory, but impaired 24-hour memory, indicating an overnight impairment of memory consolidation. In contrast, localized GluA3 knockout in the hippocampus resulted in an intact 24h memory that was resilient against SD. Indicating a role for the AMPAR subunit GluA3 for both the spatial memory consolidation, and sleep deprivation induced memory impairment. Additionally, using electrocorticography, local field potentials and electromyograms, we investigated changes in sleep. While GluA3 KO mice showed similar sleep architecture to WT littermates, their spectral power was significantly decreased in the hippocampus during both rapid eye movement sleep (REMs), and non-REMs, while spectral power was conserved in the cortex. Indicating a role for GluA3 in the oscillations during sleep. Our findings underscore the potential significance of the GluA3 subunit in sleep-mediated hippocampal memory processing, shedding new light on the complex mechanisms underlying memory consolidation.