Astrocytes contribute to remote memory formation by modulating hippocampal–cortical communication during learning

Adi Kol; Adar Adamsky; Maya Groysman; Tirzah Kreisel; Michael London; Inbal Goshen

doi:10.1038/s41593-020-0679-6

Astrocytes contribute to remote memory formation by modulating hippocampal–cortical communication during learning

Adi Kol, Adar Adamsky, Maya Groysman, Tirzah Kreisel, Michael London, Inbal Goshen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

110 Scopus citations

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 G_i-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 G_i 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
Pages (from-to)	1229-1239
Number of pages	11
Journal	Nature Neuroscience
Volume	23
Issue number	10
DOIs	https://doi.org/10.1038/s41593-020-0679-6
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.

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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.",

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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{\textquoteright}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: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

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Astrocytes contribute to remote memory formation by modulating hippocampal–cortical communication during learning

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