思い出を「選んで残す」メカニズムを解明～記憶の「安定化スイッチ」として働く意外な細胞～

2025-10-16 理化学研究所,九州大学,科学技術振興機構

本研究の概要

<関連情報>

• https://www.riken.jp/press/2025/20251016_1/index.html
• https://www.nature.com/articles/s41586-025-09619-2

アストロサイトーシス集団は記憶を安定させるための複数日間の痕跡として機能する The astrocytic ensemble acts as a multiday trace to stabilize memory

Ken-ichi Dewa,Kodai Kaseda,Aoi Kuwahara,Hideaki Kubotera,Ayato Yamasaki,Natsumi Awata,Atsuko Komori,Mika A. Holtz,Atsushi Kasai,Henrik Skibbe,Norio Takata,Tatsushi Yokoyama,Makoto Tsuda,Genri Numata,Shun Nakamura,Eiki Takimoto,Masayuki Sakamoto,Minako Ito,Takahiro Masuda & Jun Nagai
Nature  Published:15 October 2025
DOI:https://doi.org/10.1038/s41586-025-09619-2

Abstract

Recalled memories become transiently labile and require stabilization^1,2,3. The mechanism for stabilizing memories of survival-critical experiences, which are often emotionally salient and repeated, remains unclear⁴. 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 engrams⁵ 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.