A developmental brain-wide screen identifies retrosplenial cortex as a key player in the emergence of persistent memory

Abstract

Memories formed early in life are short-lived while those formed later persist. Recent work revealed that infant memories are stored in a latent state. But why they fail to be retrieved is poorly understood. Here we investigated brain-wide circuit mechanisms underlying infantile amnesia. We performed a screen that combined activity-dependent neuronal tagging at different postnatal ages, tissue clearing and light sheet microscopy. We observed striking developmental transitions in the organization of fear memory networks and changes in the activity and functional connectivity of the retrosplenial cortex (RSP) that aligned with the emergence of persistent memory. 7 days after learning, chemogenetic reactivation of tagged RSP ensembles enhanced memory in adults but not in infants. But after 33 days, reactivating infant-tagged RSP ensembles recovered forgotten memories. These studies show that RSP ensembles store latent infant memories, reveal the time course of RSP functional maturation, and suggest that immature RSP functional networks contribute to infantile amnesia.