Rac1 Signaling in Amygdala Astrocytes Regulates Fear Memory Acquisition and Retrieval
Rac1 Signaling in Amygdala Astrocytes Regulates Fear Memory Acquisition and Retrieval
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杏仁核星形胶质细胞中的 Rac1 信号传导调节恐惧记忆的获取和检索
DOI：
10.1007/s12264-021-00677-w
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发表时间：
2021-04
影响因子：
5.6
通讯作者：
Ma Lan
中科院分区：
文献类型：
--
作者：
Fan Xiao-Cen;Ma Chao-Nan;Song Jia-Chen;Liao Zhao-Hui;Huang Nan;Liu Xing;Ma Lan
星形胶质细胞在行为控制中的重要性日益受到重视，但对其动态活性在调节学习和记忆中的作用知之甚少。在本研究中，我们构建了GFAP启动子下的光活化和光灭活Ras相关C3肉毒杆菌毒素底物1（Rac 1）的AAV，这使得能够通过自由移动小鼠中的光刺激来操纵星形胶质细胞中的Rac 1活性。我们发现，无论是上调和下调星形胶质细胞Rac1活性在基底外侧杏仁核（BLA）衰减记忆获得恐惧条件反射小鼠模型。同时，在BLA的神经元激活诱导的记忆获得抑制下的星形胶质细胞Rac1活性在训练过程中的上调和下调。在对恐惧记忆提取的影响方面，我们发现BLA星形胶质细胞Rac1活性的上调和下调都损害了恐惧条件反射的记忆提取和记忆提取诱导的神经元激活。值得注意的是，星形胶质细胞Rac 1对记忆恢复的影响是可逆的。我们的研究结果表明，星形胶质细胞Rac1的正常活动是必要的神经元的激活和记忆的形成。BLA中星形胶质细胞Rac1活性的激活和失活都降低了神经元的兴奋性，从而损害了恐惧记忆的获得和提取。
The importance of astrocytes in behavior control is increasingly appreciated, but little is known about the effects of their dynamic activity in regulating learning and memory. In the present study, we constructed AAVs of photoactivatable and photoinactivatable Ras-related C3 botulinum toxin substrate 1 (Rac1) under themGFAPpromoter, which enabled the manipulation of Rac1 activity in astrocytes by optical stimulation in free-moving mice. We found that both up-regulation and down-regulation of astrocytic Rac1 activity in the basolateral amygdala (BLA) attenuated memory acquisition in a fear conditioning mouse model. Meanwhile, neuronal activation in the BLA induced by memory acquisition was inhibited under both the up- and down-regulation of astrocytic Rac1 activity during training. In terms of the impact on fear memory retrieval, we found both up- and down-regulation of BLA astrocytic Rac1 activity impaired memory retrieval of fear conditioning and memory retrieval-induced neuronal activation. Notably, the effect of astrocytic Rac1 on memory retrieval was reversible. Our results demonstrate that the normal activity of astrocytic Rac1 is necessary for the activation of neurons and memory formation. Both activation and inactivation of astrocytic Rac1 activity in the BLA reduced the excitability of neurons, and thereby impaired fear memory acquisition and retrieval.
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