Microglial activity during postnatal development is required for infantile amnesia in mice

Erika Stewart, Louisa G Zielke, Antje R de Boer, Gabrielle Guillaume Boulaire, Sarah D Power and Tomás J Ryan

PLOS Biology, 2026, vol. 24, issue 1, 1-20

Abstract: Infantile amnesia, the inability to recall episodic memories formed during early childhood, is a hallmark of postnatal brain development. Yet the underlying mechanisms remain poorly understood. This work aimed to gain a better mechanistic understanding of infantile amnesia. Microglia, specialized macrophages of the central nervous system, are known to play an important role in synaptic refinement during postnatal development and have recently been implicated in memory-related functions. Using mouse models, we identified microglia as key regulators of memory accessibility in infancy. We profiled dynamic changes in microglial morphology across the postnatal window that paralleled the onset of infantile forgetting. We found that pharmacological inhibition of microglial activity during a specific postnatal window prevents infantile amnesia for a contextual fear memory, implicating microglia as active modulators of infant memory persistence. Using activity-dependent tagging of infant encoded engram cells, we demonstrated that microglial inhibition alters engram size and engram reactivation in the amygdala and results in changes in microglia–engram cell interactions. Furthermore, we characterized a relationship between microglial dysfunction and the lack of infantile amnesia in maternal immune activation offspring. 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.Infantile amnesia limits recall of early-life memories, but its cellular basis is unclear. This study reveals that transient microglial activity during postnatal development regulates infant memory persistence and retrieval.

Date: 2026
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003538 (text/html)
https://journals.plos.org/plosbiology/article/file ... 03538&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pbio00:3003538

DOI: 10.1371/journal.pbio.3003538

Access Statistics for this article

More articles in PLOS Biology from Public Library of Science
Bibliographic data for series maintained by plosbiology ().