Learning-associated astrocyte ensembles regulate memory recall

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 recall^1-5. Astrocytes are found in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity^6-10. Moreover, astrocytes exhibit experience-dependent plasticity^11-13, 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.