Recovery of "Lost" Infant Memories in Mice

Abstract

Hippocampus-dependent, event-related memories formed in early infancy in human and non-human animals are rapidly forgotten. Recently we found that high levels of hippocampal neurogenesis contribute to accelerated rates of forgetting during infancy. Here, we ask whether these memories formed in infancy are permanently erased (i.e., storage failure) or become progressively inaccessible with time (i.e., retrieval failure). To do this, we developed an optogenetic strategy that allowed us to permanently express channelrhodopsin-2 (ChR2) in neuronal ensembles that were activated during contextual fear encoding in infant mice. We then asked whether reactivation of ChR2-tagged ensembles in the dentate gyrus was sufficient for memory recovery in adulthood. We found that optogenetic stimulation of tagged dentate gyrus neurons recovered "lost" infant memories up to 3 months following training and that memory recovery was associated with broader reactivation of tagged hippocampal and cortical neuronal ensembles.

Keywords: childhood amnesia; dentate gyrus; engram; forgetting; hippocampus; infantile amnesia; memory; optogenetics; pattern completion.