Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
Elife. 2020 Sep 1;9:e57155. doi: 10.7554/eLife.57155.
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 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 receptors (ARs) reversed the attenuation of fear memory. Furthermore, intracerebral or intraperitoneal injection of AR 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.
星形胶质细胞对神经元活动做出反应并进行调节，但它们在哺乳动物行为中的作用仍不完全清楚。特别不清楚的是，星形胶质细胞的活动是否以及如何调节情景性恐惧记忆，而这种记忆的失调会导致与恐惧相关的病理性障碍。我们生成了 大鼠，以便通过光遗传学在体内特异性地激活星形胶质细胞。我们发现，在记忆获得的时间窗口内，星形胶质细胞的激活会破坏记忆的巩固，并持续降低情景性而非提示性的恐惧记忆，同时伴有恐惧相关焦虑行为的减少。体内微透析实验表明，星形胶质细胞的光激活会增加细胞外 ATP 和腺苷的浓度。脑内腺苷 A 受体 (AR) 的阻断逆转了恐惧记忆的衰减。此外，脑内或腹腔内注射 AR 激动剂可模拟星形胶质细胞激活的作用。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理解，并为病理性与恐惧相关的障碍提供了一种新的重要治疗策略。
