Does It Matter What Keeps You Awake? Effects of Two Different Sleep Deprivation Methods on Object-Location Memory and Hippocampal c-Fos Expression in Mice

In sleep research, various sleep deprivation methods have been used to examine the effects of sleep loss on memory. However, studies often overlook the distinct impacts each method may have on activity in specific neuronal circuits and memory storage. It remains unclear whether these changes following sleep deprivation result from extended wakefulness alone or from an interaction with the nature of the waking experience. To address this question, we examined how two commonly used sleep deprivation methods in mice-gentle handling and novelty-induced sleep deprivation-affect object-location memory and hippocampal c-Fos expression. Using either method, mice were sleep deprived for 3 or 6 h immediately after training in the object-location memory task, and spatial memory performance was assessed 1 day after training. Object-location memory was impaired after 3 and 6 h of novelty-induced sleep deprivation, but only after 6 h of sleep deprivation by gentle handling. Assessing c-Fos expression in separate groups of mice immediately after 3 or 6 h of sleep deprivation showed that both methods increased c-Fos expression in the CA1 and CA3 regions after 3 h of sleep deprivation, while effects in the dentate gyrus depended on the method and blade examined. After 6 h of sleep deprivation, no significant changes in hippocampal c-Fos expression were observed regardless of the method used. Overall, our findings show that the type of experience mice have while being kept awake and the duration of sleep deprivation can have different effects on spatial memory and neuronal activity in hippocampal subregions.