Microglial inhibition in the basolateral amygdala is associated with improved socio-emotional behaviors following sleep deprivation in mice

Sleep deprivation (SD) is associated with impairments in emotional regulation and social behavior, potentially involving neuroinflammatory mechanisms. Microglia, as key regulators of neuroinflammation, have been implicated in neuropsychiatric disorders; however, their role in specific brain regions underlying SD-induced behavioral changes remains unclear. In this study, we investigated the contribution of microglia in the basolateral amygdala (BLA) to SD-induced behavioral alterations in mice. Using chemogenetic approaches, we bidirectionally manipulated microglial activity and assessed anxiety-like behavior and social interaction. We further examined associated changes in inflammatory markers, synaptic proteins, mitochondrial function, and Autophagy. We found that SD induced anxiety-like behavior and social deficits, accompanied by increased inflammatory signaling and cellular stress markers in the amygdala. Chemogenetic inhibition of BLA microglia was associated with improvements in both anxiety-like and social behaviors, whereas activation produced more limited and task-dependent effects. Microglial inhibition was also associated with reduced inflammatory markers and partial normalization of synaptic, mitochondrial, and autophagy-related changes. In contrast, global microglial depletion did not rescue behavioral deficits. These findings suggest that microglial activity in the BLA is associated with the regulation of socio-emotional behaviors following SD. The observed behavioral effects may involve coordinated changes in neuroinflammation and cellular stress-related processes.