The astrocytic ensemble acts as a multiday trace to stabilize memory

Recalled memories become transiently labile and require stabilization<sup>1-3</sup>. The mechanism for stabilizing memories of survival-critical experiences, which are often emotionally salient and repeated, remains unclear<sup>4</sup>. Here we identify an astrocytic ensemble that is transcriptionally primed by emotional experience and functionally triggered by repeated experience to stabilize labile memory. Using a novel brain-wide Fos tagging and imaging method, we found that astrocytic Fos ensembles were preferentially recruited in regions with neuronal engrams<sup>5</sup> and were more widespread during fear recall than during conditioning. We established the induction mechanism of the astrocytic ensemble, which involves two steps: (1) an initial fear experience that induces day-long, slow astrocytic state changes with noradrenaline receptor upregulation; and (2) enhanced noradrenaline responses during recall, a repeated experience, enabling astrocytes to integrate coincident signals from local engrams and long-range noradrenergic projections, which induce secondary astrocytic state changes, including the upregulation of Fos and the neuromodulatory molecule IGFBP2. Pharmacological and genetic perturbation of the astrocytic ensemble signalling modulate engrams, and memory stability and precision. The astrocytic ensemble thus acts as a multiday trace in a subset of astrocytes after experience-dependent neural activity, which are eligible to capture future repeated experiences for stabilizing memories.

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Publication Details

Journal
Nature
Published
2025-10-15
DOI
https://doi.org/10.1038/s41586-025-09619-2
Citations
15
Primary Topic
Neuroscience and Neuropharmacology Research
Type
article
Field-Weighted Citation Impact
13.64
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article

The astrocytic ensemble acts as a multiday trace to stabilize memory

Shun Nakamura, Tatsushi Yokoyama, Atsuko Komori, H. Kubotera et al.
15 citations
Nature
Neuroscience and Neuropharmacology Research
13.64
article

The astrocytic ensemble acts as a multiday trace to stabilize memory

Shun Nakamura, Tatsushi Yokoyama, Atsuko Komori, H. Kubotera, Atsushi Kasai, Henrik Skibbe, Genri Numata, Minako Ito, Jun Nagai, Takahiro Masuda, Kodai Kaseda, Masayuki Sakamoto, Ayato Yamasaki, Eiki Takimoto, Natsumi Awata, Ayumu Kuwahara, Makoto Tsuda, Norio Takata, Ken‐ichi Dewa, M Holtz
article en
15 citations

Abstract

Recalled memories become transiently labile and require stabilization<sup>1-3</sup>. The mechanism for stabilizing memories of survival-critical experiences, which are often emotionally salient and repeated, remains unclear<sup>4</sup>. Here we identify an astrocytic ensemble that is transcriptionally primed by emotional experience and functionally triggered by repeated experience to stabilize labile memory. Using a novel brain-wide Fos tagging and imaging method, we found that astrocytic Fos ensembles were preferentially recruited in regions with neuronal engrams<sup>5</sup> and were more widespread during fear recall than during conditioning. We established the induction mechanism of the astrocytic ensemble, which involves two steps: (1) an initial fear experience that induces day-long, slow astrocytic state changes with noradrenaline receptor upregulation; and (2) enhanced noradrenaline responses during recall, a repeated experience, enabling astrocytes to integrate coincident signals from local engrams and long-range noradrenergic projections, which induce secondary astrocytic state changes, including the upregulation of Fos and the neuromodulatory molecule IGFBP2. Pharmacological and genetic perturbation of the astrocytic ensemble signalling modulate engrams, and memory stability and precision. The astrocytic ensemble thus acts as a multiday trace in a subset of astrocytes after experience-dependent neural activity, which are eligible to capture future repeated experiences for stabilizing memories.

NatureVol. 648(8092)
Kyushu University (JP), Johns Hopkins University (US), Waseda University (JP), Keio University (JP), Kyoto University (JP), RIKEN Center for Brain Science (JP), Cardiovascular Institute Hospital (JP), Matsuyama University (JP), Japan Science and Technology Agency (JP), University of Tokyo Hospital (JP), Ehime University (JP), Institute of Science Tokyo (JP), Nagoya University (JP), The University of Tokyo (JP), The University of Osaka (JP)
Openalex Percentile: Top 1%
Neuroscience and Neuropharmacology Research
13.64
DOIOpen Access PDFOpenAlex
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