De-novointer-regional coactivations of pre-configured local ensembles support memory

Summary Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fear memory; however, how the inter-regional ensemble interactions support memory remains elusive. Using multi-regional large-scale electrophysiology in the afore-mentioned structures of fear-conditioned rats, we demonstrated that local ensembles activated during fear memory acquisition were inter-regionally coactivated during subsequent sleep, which relied on brief bouts of fast network oscillations. During memory retrieval, coactivations reappeared, accompanying fast oscillations. Ensembles contributing to inter-regional coactivation were configured prior to memory acquisition in the amygdala and prefrontal cortex but developed through experience in the hippocampus. Our observation suggests that elements of a given memory are instantly encoded within various brain regions in a pre-configured manner, whereas hippocampal ensembles and the network for inter-regional integration of the distributed information develop in an experience-dependent manner to form a new memory, which is consistent with hippocampal memory index hypothesis.