Distinct whole-brain c-Fos expression mapping following acute and chronic partial sleep deprivation in mice

Sleep loss constitutes a major health challenge, encompassing both acute sleep deprivation (ASD) and chronic partial sleep deprivation (CPSD). However, the differential impact of ASD and CPSD on brain-wide neuronal activity remains poorly understood. Here, we employed high-definition fluorescent micro-optical sectioning tomography (HD-fMOST) coupled with automated c-Fos quantification to systematically map global c-Fos expression in mice subjected to ASD, post-ASD recovery sleep (ASR), and CPSD. We found that 6 h of ASD broadly upregulated c-Fos expression, which was largely restored by 2 h of ASR. In contrast, 2 wk. of CPSD predominantly suppressed c-Fos but induced complex regional disparities. Cluster analysis delineated distinct activation patterns at the brain network level, whereas across conditions, similar trends were commonly observed in regions subserving related physiological functions. These findings reveal distinct whole-brain neuronal activation profiles following acute versus chronic sleep loss, highlighting potential neuromodulatory targets for treating sleep deprivation-induced dysfunction.