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 , 2 , 3 , 4 – 5 . Astrocytes are found in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity 6 , 7 , 8 , 9 – 10 . Moreover, astrocytes exhibit experience-dependent plasticity 11 , 12 – 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. A study in mice shows that learning induces c-Fos expression in a subset of astrocytes in the hippocampus, and that ensembles of these learning-associated astrocytes are involved in the recall of memories.