Immune activation state modulates retrieval of infant engrams

Abstract

AbstractInfantile amnesia is possibly the most ubiquitous form of memory loss in mammals. Despite its widespread relevance, little is known about the biological conditions for infantile amnesia to occur and its effect on the engram cells that encode a memory. We investigated how memories are stored in the brain throughout development by integrating engram labeling technology with mouse models of infantile amnesia. We discovered a sex-specific phenomenon in which male offspring in maternal immune activation models of autism spectrum disorder do not experience infantile amnesia. We rescued the same apparently forgotten infantile memories in mice by optogenetically reactivating dentate gyrus engram cells that were labeled during complex experiences in infant development. Further, we were able to permanently reinstate lost infantile memories by artificially updating the memory engram, demonstrating that infantile amnesia is a reversible process. Our findings suggest that immune activation during development modulates innate, and reversible, forgetting switches that determine whether infantile amnesia will occur.