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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\n                    <jats:italic>GFAP-ChR2-EYFP<\/jats:italic>\n                    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 A\n                    <jats:sub>1<\/jats:sub>\n                    receptors (A\n                    <jats:sub>1<\/jats:sub>\n                    Rs) reversed the attenuation of fear memory. Furthermore, intracerebral or intraperitoneal injection of A\n                    <jats:sub>1<\/jats:sub>\n                    R 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.\n                  <\/jats:p>","DOI":"10.7554\/elife.57155","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T08:00:36Z","timestamp":1598947236000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.57155","source":"Crossref","is-referenced-by-count":87,"title":["Activation of astrocytes in hippocampus decreases fear memory through adenosine A1 receptors"],"prefix":"10.7554","volume":"9","author":[{"given":"Yulan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, 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