Infantile amnesia, that curious phenomenon where young children – and animals – forget their early life experiences, has long puzzled scientists. Most adults can’t recall memories from before age 3 or 4, and similar forgetting happens in rodents during their early weeks of life. Now, a new study in mice suggests that microglia, the brain’s resident immune cells often seen as mere guardians against infection and injury, play a surprising role in this process. By shaping how memories fade in infancy, these cells may hold clues to why some neurodevelopmental conditions disrupt normal forgetting.
The research, published in PLOS Biology, focuses on how microglia influence the brain during a key postnatal period. Using mouse models, the team trained infant mice to associate a specific environment with a mild foot shock, creating a fear memory. Normally, these young mice forget the association within about a week, mirroring infantile amnesia. But when the researchers inhibited microglial activity with drugs like minocycline, the memories persisted longer than expected. The study helps paint “a clearer image of how microglia regulate memory accessibility,” revealing that these cells actively modulate whether infant memories stick around or vanish.
Microglia are known for their housekeeping duties in the brain, such as pruning excess connections between neurons during development. The researchers observed that microglial shapes and activity levels change over the infantile period, paralleling the timeline of memory loss. In brain regions like the hippocampus and amygdala, which handle context and emotion, microglia became less branched and showed reduced signs of activation as forgetting set in. “Changes in microglia activity across infant development mirrors memory retention,” the team noted in their findings.
To probe deeper, the scientists used pharmacological tools to dial down microglial function during the postnatal window. Mice treated with minocycline or a specific inhibitor of a microglia-neuron signaling pathway retained their fear memories eight days later, while untreated ones forgot. This wasn’t just generalized anxiety — the treated mice only froze in the original shock context, not new ones. Further checks showed that inhibiting microglia reduced a marker of their activation and even altered structures around neurons that stabilize brain circuits.
The team also tagged active brain cells, called engrams, that store the fear memory. In treated mice, these engrams were larger and reactivated more strongly in the amygdala during recall. Together, “these findings reveal a novel role for microglia in regulating infant memory retrieval in mice and suggest that microglial dysfunction may contribute to altered memory trajectories in neurodevelopmental disorders,” the authors concluded.
Citations
Tomás J. Ryan et al. Microglial activity during postnatal development is required for infantile amnesia in mice. Nature Communications. Published online January 20, 2026. DOI: 10.1371/journal.pbio.3003538
