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Immune activation state modulates infant engram expression across development

Sarah D. Power (Trinity College Dublin, Max Planck Institute for Human Development), Erika Stewart (Trinity College Dublin), Louisa G. Zielke (Trinity College Dublin, Maastricht University), Eric Patrick Byrne (Trinity College Dublin), Aaron Douglas (Trinity College Dublin), Clara Ortega‐de San Luis (Trinity College Dublin), Lydia Lynch (Brigham and Women's Hospital, Harvard University), Tomás J. Ryan (Canadian Institute for Advanced Research, The University of Melbourne)

Science Advances
License: CC BY

Abstract: Infantile amnesia is possibly the most ubiquitous form of memory loss in mammals. We investigated how memories are stored in the brain throughout development by integrating engram labeling technology with mouse models of infantile amnesia. Here, we found a phenomenon in which male offspring in maternal immune activation models of autism spectrum disorder do not experience infantile amnesia. Maternal immune activation altered engram ensemble size and dendritic spine plasticity. We rescued the same apparently forgotten infantile memories in neurotypical mice by optogenetically reactivating dentate gyrus engram cells labeled during complex experiences in infancy. Furthermore, we permanently reinstated lost infantile memories by artificially updating the memory engram, demonstrating that infantile amnesia is a reversible process. Our findings suggest not only that infantile amnesia is due to a reversible retrieval deficit in engram expression but also that immune activation during development modulates innate, and reversible, forgetting switches that determine whether infantile amnesia will occur.

Published on 08 Nov. 2023