Sleep deprivation is thought to affect 30% of the population worldwide. Yet our understanding of how sleep disorders develop, how to treat them, and how to prevent cognitive impairment associated with lack of sleep remains limited. Previous studies from our lab have suggested that orexinergic inputs to the hippocampus are more active when mice are sleep deprived, but whether this plays a role in the mechanism for disruption of hippocampal memories during sleep deprivation is unknown. We have used excitatory and inhibitory chemogenetic manipulations to bidirectionally modulate orexin neurons' activity in the hours following learning, using two hippocampus-dependent, sleep-dependent tasks: contextual fear conditioning and object location memory. Our preliminary data suggest that the effects of these manipulations are both sex- and task-specific. To further understand these differences, we used Brainbow viral tracing to assess whether there are morphological differences in orexinergic circuitry between males and females during sleep deprivation. Our initial findings suggest a sex difference between the stubby spine ratio and the thin spine ratio in orexin neurons, independent of behavior. To probe whether there is a functional difference, we used a GFP-mRuby viral vector to label pre-synaptic terminals and their corresponding post-synaptic partner. These studies will test the hypothesis that sex differences in orexinergic circuitry may lead to sex differences in their contribution to behavior, memory consolidation, and sleep-wake regulation.