Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors
- Zhejiang University School of Medicine, China
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
Abstract
Astrocytes respond to and regulate neuronal activity, yet their role in mammalian behavior remains incompletely understood. Especially unclear is whether, and if so how, astrocyte activity regulates contextual fear memory, the dysregulation of which leads to pathological fear-related disorders. We generated GFAP-ChR2-EYFP rats to allow the specific activation of astrocytes in vivo by optogenetics. We found that after memory acquisition within a temporal window, astrocyte activation disrupted memory consolidation and persistently decreased contextual but not cued fear memory accompanied by reduced fear-related anxiety behavior. In vivo microdialysis experiments showed astrocyte photoactivation increased extracellular ATP and adenosine concentrations. Intracerebral blockade of adenosine A1 receptors (A1Rs) reversed the attenuation of fear memory. Furthermore, intracerebral or intraperitoneal injection of A1R agonist mimicked the effects of astrocyte activation. Therefore, our findings provide a deeper understanding of the astrocyte-mediated regulation of fear memory, and suggest a new and important therapeutic strategy against pathological fear-related disorders.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all manuscript figures.Source data has been provided online at datadryad.org https://doi.org/10.5061/dryad.p8cz8w9mc
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Activation of Astrocytes in Hippocampus Decreases Fear Memory through Adenosine A1 ReceptorsDryad Digital Repository, 10.5061/dryad.p8cz8w9mc.
Article and author information
Author details
Funding
The National Key Research and Development Program (2016YFC1306700)
- Yan-Qin Yu
The National Key Research and Development Program (2016YFA0501000)
- Shumin Duan
The National Natural Science Fundation of China (31970939,31771167,31571090)
- Yan-Qin Yu
The National Natural Science Fundation of China (81527901,81821091,31490592)
- Shumin Duan
The Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2018PT31041)
- Shumin Duan
Science and technology Planning Project of Guangdong Province (2018B030331001)
- Shumin Duan
Science and technology Planning Project of Guangdong Province (2018B030331001)
- Yan-Qin Yu
Fundamental Research Funds for the Central Universitues (2019FZA7009)
- Shumin Duan
- Yan-Qin Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were approved by the Animal Advisory Committee at Zhejiang University (2019-2#) and were performed in strict accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals (2006-398#). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.
Reviewing Editor
- Margaret M McCarthy, University of Maryland School of Medicine, United States
Publication history
- Received: March 23, 2020
- Accepted: August 31, 2020
- Accepted Manuscript published: September 1, 2020 (version 1)
- Version of Record published: September 21, 2020 (version 2)
Copyright
© 2020, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors
eLife 9:e57155.
https://doi.org/10.7554/eLife.57155
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