Martin-Fernandez Mario, Jamison Stephanie, Robin Laurie M, Zhao Zhe, Martin Eduardo D, Aguilar Juan, Benneyworth Michael A, Marsicano Giovanni, Araque Alfonso
Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France.
Nat Neurosci. 2017 Nov;20(11):1540-1548. doi: 10.1038/nn.4649. Epub 2017 Sep 25.
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 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A 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.
杏仁核在恐惧和焦虑中发挥着关键作用。对杏仁核的研究主要集中在神经元功能和连接性上。星形胶质细胞与神经元存在功能上的相互作用,但其在杏仁核中的作用在很大程度上仍不为人知。我们发现,中央杏仁核内侧亚区(CeM)的星形胶质细胞决定了杏仁核回路的突触和行为输出。为了研究星形胶质细胞在杏仁核相关行为中的作用并确定潜在的突触机制,我们使用外源性或内源性信号选择性激活CeM星形胶质细胞。星形胶质细胞通过A1腺苷受体激活抑制来自基底外侧杏仁核的兴奋性突触,并通过A2A受体激活增强来自中央杏仁核外侧亚区的抑制性突触。此外,星形胶质细胞的激活降低了CeM神经元的放电率,并在恐惧条件反射范式中减少了恐惧表达。因此,我们得出结论,星形胶质细胞的活动通过选择性调节特定突触来决定恐惧反应,这表明动物行为是神经元和星形胶质细胞协同活动的结果。