Pan Han-Qing, Zhang Wen-Hua, Liao Cai-Zhi, He Ye, Xiao Zhi-Ming, Qin Xia, Liu Wei-Zhu, Wang Na, Zou Jia-Xin, Liu Xiao-Xuan, Pan Bing-Xing
Department of Biological Science, School of Life Sciences, Nanchang University, Nanchang, China.
Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang, China.
Front Neurosci. 2020 Apr 17;14:299. doi: 10.3389/fnins.2020.00299. eCollection 2020.
Chronic or prolonged exposure to stress ranks among the most important socioenvironmental factors contributing to the development of neuropsychiatric diseases, a process generally associated with loss of inhibitory tone in amygdala. Recent studies have identified distinct neuronal circuits within the basolateral amygdala (BLA) engaged in different emotional processes. However, the potential circuit involved in stress-induced dysregulation of inhibitory tones in BLA remains elusive. Here, a transgenic mouse model expressing yellow fluorescent protein under control of the Thy1 promoter was used to differentiate subpopulations of projection neurons (PNs) within the BLA. We observed that the tonic inhibition in amygdala neurons expressing and not expressing Thy1 (Thy1+/-) was oppositely regulated by chronic social defeat stress (CSDS). In unstressed control mice, the tonic inhibitory currents were significantly stronger in Thy1- PNs than their Thy1+ counterparts. CSDS markedly reduced the currents in Thy1- projection neurons (PNs), but increased that in Thy1+ ones. By contrast, CSDS failed to affect both the phasic A-type γ-aminobutyric acid receptor (GABAR) currents and GABAR currents in these two PN populations. Moreover, chronic corticosterone administration was sufficient to mimic the effect of CSDS on the tonic inhibition of Thy1+ and Thy1- PNs. As a consequence, the suppression of tonic GABAR currents on the excitability of Thy1- PNs was weakened by CSDS, but enhanced in Thy1+ PNs. The differential regulation of chronic stress on the tonic inhibition in Thy1+ and Thy1- neurons may orchestrate cell-specific adaptation of amygdala neurons to chronic stress.
长期或慢性暴露于应激状态是导致神经精神疾病发生的最重要的社会环境因素之一,这一过程通常与杏仁核抑制性张力丧失有关。最近的研究已经确定了基底外侧杏仁核(BLA)内参与不同情绪过程的独特神经回路。然而,参与应激诱导的BLA抑制性张力失调的潜在回路仍然不清楚。在这里,利用在Thy1启动子控制下表达黄色荧光蛋白的转基因小鼠模型来区分BLA内投射神经元(PNs)的亚群。我们观察到,慢性社会挫败应激(CSDS)对表达和不表达Thy1(Thy1+/-)的杏仁核神经元的紧张性抑制有相反的调节作用。在未受应激的对照小鼠中,Thy1- PNs的紧张性抑制电流明显强于Thy1+ PNs。CSDS显著降低了Thy1-投射神经元(PNs)的电流,但增加了Thy1+ PNs的电流。相比之下,CSDS对这两个PN群体的相位A型γ-氨基丁酸受体(GABAR)电流和GABAR电流均无影响。此外,长期给予皮质酮足以模拟CSDS对Thy1+和Thy1- PNs紧张性抑制的作用。因此,CSDS减弱了紧张性GABAR电流对Thy1- PNs兴奋性的抑制作用,但增强了Thy1+ PNs的抑制作用。慢性应激对Thy1+和Thy1-神经元紧张性抑制的差异调节可能协调杏仁核神经元对慢性应激的细胞特异性适应。