Learning-associated astrocyte ensembles regulate memory recall.

The physical manifestations of memory formation and recall are fundamental questions that remain unresolved(1). 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.