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Rac1 Signaling in Amygdala Astrocytes Regulates Fear Memory Acquisition and Retrieval

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Abstract

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 the mGFAP promoter, 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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Acknowledgements

This work was supported by Grants from the China Postdoctoral Science Foundation (BX20180070 and 2019M661347), and the National Natural Science Foundation of China (31930046 and 31771176).

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  1. Xiao-Cen Fan and Chao-Nan Ma contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences, Institutes of Brain Science, Fudan University, Shanghai, 200032, China

    Xiao-Cen Fan, Chao-Nan Ma, Jia-Chen Song, Zhao-Hui Liao, Nan Huang, Xing Liu & Lan Ma

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  1. Xiao-Cen Fan
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Fan, XC., Ma, CN., Song, JC. et al. Rac1 Signaling in Amygdala Astrocytes Regulates Fear Memory Acquisition and Retrieval. Neurosci. Bull. 37, 947–958 (2021). https://doi.org/10.1007/s12264-021-00677-w

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  • DOI: https://doi.org/10.1007/s12264-021-00677-w

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