Hippocampal-cortical coupling dynamics drive system consolidation of remote memory

Abstract

System consolidation transforms temporary hippocampal representation of memory into long-term storage in cortex. The underlying neural substrate, however, remains enigmatic. Here, we tracked the spatiotemporal evolution of hippocampus (HPC)-cortex local field potentials and single-neuron spikes in behaving animals during fear memory formation. During learning, HPC fast gamma exhibited a progressive phase shift relative to PFC theta oscillations, with gamma power aligning to progressively later phases of the PFC theta cycle. Strikingly, a related phase-shifted coupling pattern re-emerged during subsequent consolidation in association with hippocampal sharp-wave ripples and transient PFC spindle events during NREM sleep. Across this process, interregional interactions evolved from HPC-driven cortical gamma coherence at recent stages to PFC-mediated cortical low-frequency coherence at remote stages. Using closed-loop optogenetic perturbations, we demonstrated a stepwise causal chain of coupling events underlying remote memory formation. Our study revealed HPC-PFC coupling phase shift as a feasible substrate mediating recent-to-remote transformation of memory.