Communication between the hippocampus and the prefrontal cortex (HPC, PFC) is necessary for consolidating memories during both wakefulness and sleep. The activity-regulated gene Arc/Arg3.1 is essential in mediating memory consolidation1 and has been shown to influence memory-associated network activity2,3.We here investigate the impact of hippocampal Arc/Arg3.1 expression on network dynamics between the HPC and PFC during spontaneous brain state changes in sleep induced by urethane anesthesia. We used virus-mediated conditional deletion of Arc/Arg3.1 in the hippocampus and silicon probes to record local field potentials (LFPs) and spike activity from both regions simultaneously. We also used a range of analysis methods to infer functional connectivity between the HPC and PFC.Our study underlines the important role of Arc/Arg3.1 in modulating hippocampal activity and its effects on the communication between the hippocampus and prefrontal cortex. Our findings suggest that deleting hippocampal Arc/Arg3.1 alters neural firing in both regions and modifies the functional connectivity between the hippocampus and prefrontal cortex.1. Plath, N., Ohana, O. . . Kuhl, D. (2006). Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.2. Gao, X. . . Ohana, O. (2018). Arc/Arg3.1 mediates a critical period for spatial learning and hippocampal networks.3. Gao, X. . . Ohana, O. (2019). Disturbed prefrontal cortex activity in the absence of schizophrenia-like behavioral dysfunction in Arc/Arg3.1 deficient mice