Activation of astrocytes in hippocampus decreases fear memory through adenosine A(1) receptors.
Activation of astrocytes in hippocampus decreases fear memory through adenosine A(1) receptors.
复制标题
海马星形胶质细胞的激活通过腺苷 A1 受体减少恐惧记忆
作者：
Li Y;Li L;Wu J;Zhu Z;Feng X;Qin L;Zhu Y;Sun L;Liu Y;Qiu Z;Duan S;Yu YQ
星形胶质细胞对神经元活动做出反应并调节神经元活动，但它们在哺乳动物行为中的作用仍不完全清楚。尤其不清楚的是，星形胶质细胞的活动是否调节情境恐惧记忆，如果调节的话，如何调节情境恐惧记忆，其失调会导致病理性恐惧相关疾病。我们生成了 GFAP-ChR2-EYFP 大鼠，通过光遗传学在体内特异性激活星形胶质细胞。我们发现，在时间窗口内获得记忆后，星形胶质细胞激活会破坏记忆巩固，并持续减少情境但无提示的恐惧记忆，同时减少与恐惧相关的焦虑行为。体内微透析实验表明星形胶质细胞光活化增加了细胞外 ATP 和腺苷浓度。脑内阻断腺苷 A1 受体 (A1R) 可逆转恐惧记忆的减弱。此外，脑内或腹膜内注射 A1R 激动剂模拟了星形胶质细胞激活的效果。因此，我们的研究结果提供了对星形胶质细胞介导的恐惧记忆调节的更深入的了解，并提出了一种针对病理性恐惧相关疾病的新的重要治疗策略。
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.