The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A 1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A 2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.
Bibliographical noteFunding Information:
We thank J. Chen (UCSD, La Jolla, California, USA) for providing IP3R2− mice, and W. Buño, G. Perea, M. Navarrete and A. Covelo for helpful comments. This work was supported by NIH–NINDS (R01NS097312-01 to A.A.), the Human Frontier Science Program (Research Grant RGP0036/2014 to A.A. and G.M.), INSERM (to G.M.), Fondation pour la Recherche Medicale (DRM20101220445 to G.M.) and the China Scholarship Council (to Z.Z.). We thank the MnDRIVE Optogenetics Core at the University of Minnesota for technical support, and B. Roth and the UNC Vector Core (Chapel Hill, North Carolina, USA) for providing the Gq-DREADD adeno-associated virus.