PROJECT SUMMARY Learning and memory are fundamental cognitive functions that allow us to learn from the environment around us. Memory is the ability to store and recall information essential to everyday life. An indispensable property of memory is its stable storage, allowing for the recall of memories over extended periods of time. Yet the physiological mechanisms underlying the stable storage of memories for such a long-lasting time remain to be elucidated. Memory formation involves two stages, encoding, and consolidation. After encoding, the consolidation process solidifies these neuronal traces into long-lasting memories. Consolidation is a progressive process, starting with immediate consolidation that, over time, becomes long-term consolidation. The hippocampus (HPC) is a brain region fundamental to memory formation and immediate consolidation. As consolidation continues, the HPC offloads memories to the cortex, eventually becoming independent of the HPC. The HPC consolidation of memories involves a highly synchronous network event called a sharp-wave ripple (SWR). During SWRs, memory traces that represent a particular experience are replayed in a compressed manner, which is thought to consolidate these neuronal representations through synaptic plasticity. Yet, it is unknown how information from the HPC is transferred to the cortex during SWRs during immediate consolidation. A cortical region also involved in memory is the prefrontal cortex (PFC). Both the HPC and PFC are involved in spatial memory, making it an ideal behavior to investigate the transfer of HPC information to the PFC during immediate consolidation. The respective contribution of SWRs and local cortical circuit dynamics for immediate memory consolidation remains unknown. Furthermore, the circuit and cellular changes during immediate consolidation are not fully understood. This proposal targets these exact questions by 1) directly testing whether SWRs transfer information to the PFC necessary for immediate consolidation; 2) identifying the PFC neuronal assembly modifications during SWRs underlying immediate consolidation; and 3) elucidating the local PFC circuitry mechanisms that regulate these neuronal assembly changes during immediate consolidation. The aims of this proposal will directly test whether communication between HPC and PFC that occurs during SWRs is crucial for immediate memory consolidation and how local processes in the PFC evolve during memory consolidation. This work aligns with NIMH’s mission to understand the mechanisms of learning and memory at a system level by investigating the interactions between brain regions that might underlie these functions.