The astrocytic ensemble acts as a multiday trace to stabilize memory

• 成果类型: Article
• 署名作者: Dewa, Ken-ichi; Kaseda, Kodai; Kuwahara, Aoi; Kubotera, Hideaki; Yamasaki, Ayato; Awata, Natsumi; Komori, Atsuko; Holtz, Mika A.; Kasai, Atsushi; Skibbe, Henrik; Takata, Norio; Yokoyama, Tatsushi; Tsuda, Makoto; Numata, Genri; Nakamura, Shun; Takimoto, Eiki; Sakamoto, Masayuki; Ito, Minako; Masuda, Takahiro; Nagai, Jun
• 署名单位: RIKEN; Waseda University; Kyushu University; Kyushu University; Nagoya University; University of Osaka; Japan Science & Technology Agency (JST); RIKEN; Matsuyama University; Keio University; Kyoto University; Kyoto University; Kyoto University; Kyoto University; Kyushu University; Kyushu University; University of Tokyo; University of Tokyo; Institute of Science Tokyo; Johns Hopkins University; Johns Hopkins Medicine; Japan Science & Technology Agency (JST)
• 刊物名称: NATURE
• ISSN/ISSBN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-025-09619-2
• 发表日期: 2025-12-04
• 关键词: in-vivo; reconsolidation; mechanisms; mouse; consolidation; disruption; plasticity; blockade

摘要

Recalled memories become transiently labile and require stabilization1, 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.