Cortical-hippocampal dynamics during sharp-wave ripples evolve across learning

Memories become stabilized through a process called consolidation. The consolidation of episodic memory, memory of events and experiences, is reliant on the hippocampus. While lesions to the hippocampus impair the ability to form new memories, stabilized long-term memories remain largely intact, suggesting the hippocampus is not necessary for the long-term storage of memories. Instead, memories are thought to become cortical dependent for long-term storage in a process called systems consolidation. Sharp-wave ripples (ripples), neural oscillations predominantly in CA1 of the hippocampus, are critical for this process. During sleep, ripples mark the reactivation of hippocampal neurons and coincide with the reactivation of cortical neurons that were active during wakefulness. Disrupting or enhancing ripple-mediated reactivation during sleep impairs or improves memory formation, respectively. Yet, how ripple-mediated reactivation manifests across distinct experiences remains unknown. Recently, researchers have identified two anatomically distinct CA1 pyramidal sublayers that differ in function during ripples: superficial (CA1sup) and deep (CA1deep). Namely, CA1sup neurons primarily encode contextual and spatial information, whereas CA1deep neurons respond more to environmental features such as reward or sensory cues. These differences may enable functional diversity of the content of ripples during sleep to promote memory specificity. Despite this, the mechanism which differentially drives these sublayers during ripples remains unclear. Here we uncover a novel line of communication between the anterior cingulate cortex (ACC) and CA1sup neurons during ripples and sleep, which is modified following learning. Specifically, utilizing a generalized linear model decoder, we demonstrate the pre-existence of ACC-to-CA1sup communication, which is suppressed during new learning and subsequent sleep, suggesting that ACC activity reallocates the contribution of CA1sup neurons during memory acquisition and consolidation. Further supporting this notion, we found that optogenetic stimulations of the ACC preferentially suppressed CA1sup neurons while activating a unique subset of CA1 interneurons. Overall, this work reveals a distinct cortical-hippocampal pathway that reconfigures CA1 sublayer dynamics across learning and sleep, potentially promoting the formation of specific and stable memories.