Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence

Kuan Zhang, Rita Förster, Wenjing He, Xiang Liao, Jin Li, Chuanyan Yang, Han Qin, Meng Wang, Ran Ding, Ruijie Li, Tingliang Jian, Yanhong Wang, Jianxiong Zhang, Zhiqi Yang, Wenjun Jin, Yonghai Zhang, Song Qin, Yacheng Lu, Tao Chen, Jillian StobartBruno Weber, Helmuth Adelsberger, Arthur Konnerth, Xiaowei Chen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Memory persistence is a fundamental cognitive process for guiding behaviors and is considered to rely mostly on neuronal and synaptic plasticity. Whether and how astrocytes contribute to memory persistence is largely unknown. Here, by using two-photon Ca2+ imaging in head-fixed mice and fiber photometry in freely moving mice, we show that aversive sensory stimulation activates α7-nicotinic acetylcholine receptors (nAChRs) in a subpopulation of astrocytes in the auditory cortex. We demonstrate that fear learning causes the de novo induction of sound-evoked Ca2+ transients in these astrocytes. The astrocytic responsiveness persisted over days along with fear memory and disappeared in animals that underwent extinction of learned freezing behavior. Conditional genetic deletion of α7-nAChRs in astrocytes significantly impaired fear memory persistence. We conclude that learning-acquired, α7-nAChR-dependent astrocytic responsiveness is an integral part of the cellular substrate underlying memory persistence.

Original languageEnglish
Pages (from-to)1686-1698
Number of pages13
JournalNature Neuroscience
Volume24
Issue number12
DOIs
StatePublished - Dec 2021

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