A hallmark of Alzheimer’s disease (AD) pathology is amyloid plaques which can lead to neuroinflammation, cellular dysfunctions as well as altered neuronal activity. Both AD patients and mouse models exhibit abnormal neural oscillations, including altered gamma oscillations, hippocampal sharp wave-ripples (SWRs) and cortical sleep spindles. Although these oscillations play a role in memory formation and consolidation, it remains poorly understood how abnormal oscillations relate to novel experiences. Here we show that deficits in SWRs are experience-dependent in an AD mouse model. We performed in vivo electrophysiological recordings in a freely behaving condition to characterize hippocampal SWRs and cortical sleep spindles across the sleep-wake cycle in 5xFAD mice. Although SWRs during non-rapid eye movement (NREM) sleep increased just after exposure to a novel environment or exploration of a novel object in littermate controls, this increase was significantly diminished in AD mice. On the other hand, cortical sleep spindles and their co-occurrence with SWRs were not altered in AD mice, suggesting that thalamocortical functions are spared from amyloid pathology. To examine if the diminished SWRs are associated with abnormal cholinergic tone in the hippocampus, we are currently performing electrophysiology in a freely behaving condition while optically monitoring hippocampal acetylcholine levels across sleep-wake cycles. Our findings to date suggest that hippocampal SWRs can be a target for neuromodulation-based treatment of AD.