The impact of sleep pressure and timing on hippocampal reactivation and replay

/Project Summary The circadian rhythm has strong effects on cognition and memory. There is also strong evidence that the activities of neurons during sleep are important for the memory function of the brain. Until recently, little was known about why delaying these activities for a prolonged period of wakefulness (commonly known as “sleep loss”) should have an enduring negative impact on memory, especially given the brain’s general capacity to restore itself during an eventual “recovery sleep”. Recently, by recording from large populations of hippocampal neurons in behaving and sleeping rodents, we found that the reactivation and replay of neuronal ensembles in the hippocampus during sharp-wave ripple events were significantly diminished during recovery sleep compared to in sleep immediately following behavior on a maze, suggesting that prolonged waking during the inactive cycle, when animals normally sleep, impairs the capacity of the hippocampus to generate the patterns widely considered most important for the consolidation of memories. However, key questions remain concerning how these sleep-dependent effects interact with the circadian cycle—known to impact learning and memory—and the optimal times and durations for waking and sleep for reactivations and replays that are critical to hippocampal function. In this proposal, we investigate how different periods of extended waking, at different phases of the circadian cycle, plus arousal enhanced by caffeine, impact hippocampal neuronal firing patterns during sharp-wave ripples, in both the awake state and the subsequent sleep. We further investigate the impact of enhancing these events by optogenetically prolonging their duration to test their impact on hippocampus-dependent memory. In sum, this work will help elucidate how sleep pressure and circadian timing interact to impact on hippocampal function and influence the systems-level firing patterns that are considered to support the hippocampal role in memory. Project Number: 1R01NS147469-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: KAMRAN DIBA (+1 co-PI) | Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR, ANN ARBOR, MI | Award Amount: $532,314 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 ICN-N (92)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11319945