Data from: Glucocorticoid induces incoordination between glutamatergic and GABAergic neurons in the amygdala

Background: Stressful life leads to mood disorders. Chronic mild stress is presumably major etiology for depression, and acute severe stress leads to anxiety. These stressful situations may impair hypothalamus-pituitary-adrenal axis and in turn induce synapse dysfunction. However, it remains elusive how the stress hormones mess up subcellular compartments and interactions between excitatory and inhibitory neurons, which we have investigated in mouse amygdala, a structure related to emotional states. Methods and Results: Dexamethasone was chronically given by intraperitoneal injection once a day for one week or was acutely washed into the brain slices. The neuronal spikes and synaptic transmission were recorded by whole-cell patching in amygdala neurons of brain slices. The chronic or acute administration of dexamethasone downregulates glutamate release as well as upregulates GABA release and GABAergic neuron spiking. The chronic administration of dexamethasone also enhances the responsiveness of GABA receptors. Conclusion: The upregulation of GABAergic neurons and the downregulation of glutamatergic neurons by glucocorticoid impair their balance in the amygdala, which leads to emotional disorders during stress.

背景：应激性生活事件可诱发心境障碍。慢性轻度应激被认为是抑郁症的主要病因，而急性重度应激则会引发焦虑障碍。此类应激事件可损伤下丘脑-垂体-肾上腺轴（hypothalamus-pituitary-adrenal axis），进而诱发突触功能异常。然而，应激激素如何扰乱亚细胞区室及兴奋性与抑制性神经元间的相互作用，这一问题仍有待阐明，我们在与情绪调控相关的脑结构——小鼠杏仁核（amygdala）——中开展了相关研究。
方法与结果：本研究采用两种给药方案：一是每日单次腹腔注射地塞米松（dexamethasone），连续给药一周以建立慢性给药模型；二是将地塞米松急性灌流至脑片浴液中。采用全细胞膜片钳（whole-cell patching）技术记录脑片杏仁核神经元的动作电位与突触传递活动。结果显示，慢性或急性给予地塞米松均可下调谷氨酸（glutamate）释放水平，同时上调γ-氨基丁酸（GABA）释放量及GABA能神经元的锋电位发放；慢性给予地塞米松还可增强GABA受体（GABA receptor）的响应敏感性。
结论：糖皮质激素（glucocorticoid）通过上调GABA能神经元活性、下调谷氨酸能神经元（glutamatergic neuron）活性，破坏杏仁核内两类神经元的功能平衡，进而在应激状态下引发情绪障碍。