Local Neuronal Ensembles That Coreactivate across Regions during Sleep Are Preferentially Stabilized

Neuronal ensembles, which represent coordinated activity patterns within individual brain regions, play crucial roles in memory. While local ensembles dynamically change in response to experience, factors influencing the stability of neuronal ensemble compositions remain largely unknown. In this study, we analyzed the dynamics of neuronal ensembles in the prelimbic cortex layer 5 (PL5), basolateral nucleus of the amygdala (BLA), and ventral hippocampus CA1 region (vCA1) during conditioning, extinction, retention of extinction, and interleaving sleep epochs in fear-conditioned male rats. We found that ensemble compositions in the PL5 were more stable than those in the BLA and vCA1. Ensemble reactivation during non-rapid eye movement (NREM) sleep following extinction sessions did not fully explain whether extinction-related ensembles were preserved until the retention-of-extinction sessions. Although the extinction sessions did not affect the number of ensemble pairs that were inter-regionally coactivated during NREM sleep, patterns of inter-regional ensemble coactivation were reorganized after extinction sessions, suggesting that extinction modifies the fine-scale structure of inter-regional networks. Notably, extinction-related ensembles that coactivated with those in other regions during post-extinction NREM sleep were more likely to be preserved until the retention-of-extinction sessions. In post-extinction NREM sleep, the preserved extinction-related ensembles contributing to inter-regional coactivation were activated more frequently during fast network oscillations. These findings suggest that local ensembles contributing to broader inter-regional activity are preferentially stabilized, supporting a systems-level mechanism of memory consolidation.