Learning-associated astrocyte ensembles regulate memory recall

Michael R. Williamson, Wookbong Kwon, Junsung Woo, Yeunjung Ko, Ehson Maleki, Kwanha Yu, Sanjana Murali, Debosmita Sardar and Benjamin Deneen ()
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Michael R. Williamson: Baylor College of Medicine
Wookbong Kwon: Baylor College of Medicine
Junsung Woo: Baylor College of Medicine
Yeunjung Ko: Baylor College of Medicine
Ehson Maleki: Baylor College of Medicine
Kwanha Yu: Baylor College of Medicine
Sanjana Murali: Baylor College of Medicine
Debosmita Sardar: Baylor College of Medicine
Benjamin Deneen: Baylor College of Medicine

Nature, 2025, vol. 637, issue 8045, 478-486

Abstract: Abstract The physical manifestations of memory formation and recall are fundamental questions that remain unresolved1. At the cellular level, ensembles of neurons called engrams are activated by learning events and control memory recall1–5. Astrocytes are found in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity6–10. Moreover, astrocytes exhibit experience-dependent plasticity11–13, although whether specific ensembles of astrocytes participate in memory recall remains obscure. Here we show that learning events induce c-Fos expression in a subset of hippocampal astrocytes, and that this subsequently regulates the function of the hippocampal circuit in mice. Intersectional labelling of astrocyte ensembles with c-Fos after learning events shows that they are closely affiliated with engram neurons, and reactivation of these astrocyte ensembles stimulates memory recall. At the molecular level, learning-associated astrocyte (LAA) ensembles exhibit elevated expression of nuclear factor I-A, and its selective deletion from this population suppresses memory recall. Taken together, our data identify LAA ensembles as a form of plasticity that is sufficient to provoke memory recall and indicate that astrocytes are an active component of the engram.

Date: 2025
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DOI: 10.1038/s41586-024-08170-w

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