HIDDEN MEMORIES: ENGRAM COMPETITION PREVENTS ACCESS TO INFANT MEMORIES

Forgetting of our earliest memories is a near-universal phenomenon termed infantile amnesia. Although episodic memories formed before the age of three in humans are inaccessible to natural recall, experimental evidence in mice indicates that infant memories persist and can be artificially reactivated, updated, and reinstated in adulthood. However, the question of what causes infantile amnesia at an engram level remains open. Here, we combined contextual fear conditioning to assess infantile amnesia with engram-labelling techniques and opto- and chemogenetics to identify and manipulate interfering memory ensembles. We found that infant engrams were reactivated above chance levels despite the absence of behavioural recall. Compared to adult memories, infant engrams exhibited reduced competitive advantage during recall, as indicated by altered proportions of c-Fos–positive engram to non-engram cells in the dentate gyrus. Homecage engram cells labelled during the infantile amnesia window showed substantial reactivation during recall of the fear-conditioning context. Inhibiting the activity of this amnesia-related ensemble enabled recall of the original contextual fear memory formed in infancy. Conversely, activating an alternative engram during recall of an adult memory reduced freezing behaviour. We further observed that memories formed in infancy are susceptible to retroactive interference, another form of natural forgetting. Similar to infantile amnesia, inhibiting the activity of non-engram cells at recall enabled infant memory retrieval. Together, these findings indicate that infantile amnesia arises not from engram loss or silencing, but from increased interference by competing neuronal populations during recall. Enhancing the signal-to-noise ratio at retrieval enables access to otherwise inaccessible infant memories.