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Authors & Affiliations
Louisa Zielke, Erika Stewart, Petra Omejec, Sarah Power, Andrin Abegg, Shiva Tyagarajan, Tomás Ryan
Abstract
Early episodic and contextual memories are forgotten despite their distinct impact on personality development and future behaviour. This phenomenon, termed infantile amnesia, is widely seen in humans and is conserved across other altricial species. In previous years it has become evident that infant memories are stored through the plasticity of neuronal ensembles, forming engrams that remain present in the brain in a latent state once forgotten. Recently, it has been shown that alterations in brain development caused by maternal immune activation (MIA) lead to infant memory retention in male offspring. However, it remains unknown what is causing infantile amnesia. Different lines of research have suggested that some forms of natural and pathological forgetting are due to the competition of multiple memory ensembles. We hypothesise that memory engram competition may also contribute to the forgetting of infant memories during development. Here we combined contextual fear conditioning (CFC) with engram labelling techniques and chemogenetics to identify and manipulate competing memory ensembles in mice throughout development. Our results demonstrate that infantile amnesia is accompanied by increased activation of non-engram cells. We observed no increase in inhibitory synaptic puncta on engram cells. Furthermore, artificial inhibition of these interfering engrams allows for infant memory recall. Lastly, we found that MIA offspring were resistant to retroactive interference, another form of natural forgetting. Together, these results indicate that infantile amnesia may be due to interfering memories formed during development competing with the expression of infant memory engrams.