Publication Date

1-1-2025

Journal

Nature

DOI

10.1038/s41586-024-08170-w

PMID

39506118

PMCID

PMC11924044

PubMedCentral® Posted Date

5-1-2025

PubMedCentral® Full Text Version

Author MSS

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 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; however 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, which subsequently regulates hippocampal circuit function. Intersectional, c-Fos based labeling of astrocyte ensembles after learning events reveals that they are closely affiliated with engram neurons, while re-activation of these astrocyte ensembles stimulates memory recall. At the molecular level, learning-associated astrocyte ensembles exhibit elevated expression of NFIA and its selective deletion from this population suppresses memory recall. Together, our studies identify learning-associated astrocyte ensembles as a new form of plasticity that is sufficient to provoke memory recall, while implicating astrocytes as an active component of the engram.

Keywords

Animals, Astrocytes, Mice, Mental Recall, Male, Hippocampus, Proto-Oncogene Proteins c-fos, Learning, Neurons, Neuronal Plasticity, Female, Mice, Inbred C57BL

Published Open-Access

yes

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.