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Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors

Citation

Yu, Yan-Qin et al. (2020), Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors, Dryad, Dataset, https://doi.org/10.5061/dryad.p8cz8w9mc

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.

Funding

National Key Research and Development Program, Award: 2016YFC1306700

National Natural Science Foundation of China, Award: 31970939

Chinese Academy of Medical Sciences, Award: Non-profit Central Research Institute Fund 2018PT31041

Science and Technology Planning Project of Guangdong Province, Award: 2018B030331001

Fundamental Research Funds for the Central Universitues, Award: 2019FZA7009

CAMS Innovation Fund for Medical Science, Award: 2019-I2M-5-057