Sleep deprivation differentially recruits amygdala subregions in male and female mice

Sleep deprivation (SD) acutely increases negative affect, and chronic insufficient sleep is associated with an increased risk of depression. Since the amygdala regulates both emotional processing and sleep, and SD dysregulates amygdalar function, amygdala functionality may link sleep loss to emotional outcomes. To better understand this, the specific sleep-impacted amygdalar nuclei need to be fully defined. To determine the impact of acute sleep loss on the relative activation of specific amygdalar regions, we screened for the neuronal activity marker c-Fos in wildtype mice that slept undisturbed, underwent 4-h SD, or 4-h SD with 2-h recovery sleep (RS). Application of whole-brain clearing and automated cell counting identified increased c-Fos expression within the cortical subplate of both male and female mice that was localized to amygdalar regions. As the amygdala comprises multiple distinct subnuclei, we parcellated and quantified c-Fos expression within each amygdalar subnucleus. Interestingly, we found that SD-induced differential c-Fos expression patterns between sexes. In male mice, SD increased c-Fos expression across several amygdalar subnuclei, which largely reversed with RS. By contrast, SD in females increased c-Fos expression only in the anterior basolateral amygdala and the intercalated amygdala, and both subnuclei remained activated even with RS. These findings highlight sex-specific spatial distribution of SD-activated amygdala cells, which may contribute to differences in emotional processing following sleep loss and offer potential anatomical targets for mitigating SD-related mood deficits.