How the brain is able to simultaneously support learning of new information without corrupting existing memories remains an unanswered question. Systems consolidation theory argues that successful memory consolidation requires integrating new learning - acquired in the highly plastic hippocampus - into more stable cortical networks. Thoroughly testing this theory requires the ability to track long-term, learning-related changes in cortical neurons across multiple days, which has been difficult until recently due to technological limitations. While advances in calcium imaging now permit the long-term tracking of neuron activity in vivo, its limited temporal resolution prevents the study of one likely candidate for hippocampal-cortical interactions: high-frequency hippocampal oscillations dubbed sharp-wave ripples (SWRs) that occur during slow-wave sleep (SWS). I propose directly testing the hypothesis that hippocampal-cortical interactions during sleep facilitate the induction and maintenance of learning related plasticity. To address this hypothesis, I propose combining electrophysiological recordings in the hippocampus with long-term calcium imaging in the prefrontal cortex of rodents, a region necessary for long-term memory recall. In Aim 1, I will characterize how hippocampal SWR activity during sleep influences long-term, learning-related changes in prefrontal neuron activity following the acquisition of an associative learning task. In Aim 2, I will utilize sleep deprivation to test the relationship between sleep, long-term memory, and prefrontal neuron plasticity. In Aim 3, I will characterize the time course of the hippocampal-prefrontal dialog supporting the gradual acquisition of a more difficult long-term memory task. Sleep disturbances are endemic to today’s society, emerge during normal aging, and slowly increase through the course of Alzheimer’s Disease (AD). Moreover, sleep deprivation can exacerbate the prevalence of tau and amyloid beta, two hallmark AD pathologies, in the hippocampus and cortex. Understanding how sleep influences hippocampal-cortical coordination and long-term plasticity could provide valuable insights into memory deficits caused by sleep deprivation, normal aging, and AD, which could guide interventions to improve memory outcomes.