Abstract
Remote memories depend on coordinated activity in the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes sense and modify neuronal activity, but their role in remote memory is scarcely explored. We expressed the Gi-coupled designer receptor hM4Di in CA1 astrocytes and discovered that astrocytic manipulation during learning specifically impaired remote, but not recent, memory recall and decreased activity in the anterior cingulate cortex (ACC) during retrieval. We revealed massive recruitment of ACC-projecting CA1 neurons during memory acquisition, which was accompanied by the activation of ACC neurons. Astrocytic Gi activation disrupted CA3 to CA1 communication in vivo and reduced the downstream response in the ACC. In behaving mice, it induced a projection-specific inhibition of CA1-to-ACC neurons during learning, which consequently prevented ACC recruitment. Finally, direct inhibition of CA1-to-ACC-projecting neurons spared recent and impaired remote memory. Our findings suggest that remote memory acquisition involves projection-specific functions of astrocytes in regulating CA1-to-ACC neuronal communication.
Original language | American English |
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Pages (from-to) | 1229-1239 |
Number of pages | 11 |
Journal | Nature Neuroscience |
Volume | 23 |
Issue number | 10 |
DOIs | |
State | Published - 1 Oct 2020 |
Bibliographical note
Funding Information:We thank the entire Goshen Lab for their support. A.K. is supported by the JBC GOLD Scholarship. A.A. is supported by the Adams fellowship. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 803589 to I.G.). I.G. is also supported by the Israel Science Foundation (ISF grant no. 1815/18), the Israeli Centers of Research Excellence Program (center no. 1916/12) and Canada–Israel grants (CIHR–ISF, grant no. 2591/18). M.L. is a Sachs Family Lecturer in Brain Science and is supported by the ISF (ISF grant no. 1024/17) and the Einstein Foundation. We thank Y. Ziv, A. Citri, I. Slutsky and A. Doron for their critical reading of the manuscript.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.