Central Neural Mechanisms of the Defense Response against Stressor

我们以前表明，防御反应引起的应激减弱prepro-orexin基因敲除小鼠和orexin神经元消融小鼠，我们提出，orexin作为一个主开关内的多个传出通路，介导的防御反应。在这项研究中，我们试图确定杏仁核（AMG）或终纹床核（BNST）的兴奋是否激活含食欲素的神经元，以及这些神经元是否在引发对刺激的心肺反应中是必不可少的。在麻醉小鼠中，将GABA-A受体拮抗剂荷包牡丹碱微量注射到AMG或BNST中，电刺激诱导血压、心率、呼吸频率和潮气量同时增加的部位。在任一部位注射荷包牡丹碱可诱导野生型小鼠产生持久的剂量依赖性心肺兴奋。相反，食欲素神经元已被消融的小鼠在AMG激活后没有表现出这种反应，而在BNST激活后只有很小的反应。食欲素和c-Fos的双重免疫组织化学染色显示，注射荷包牡丹碱可诱导下丘脑内侧部显著增加表达c-Fos的食欲素阳性神经元的数量（AMG中58.2 ± 6.4%和BNST中66.4 ± 6.6%，各n=3）比媒介物（AMG中18.2 ± 4.4%和BNST中28.3 ± 2.1%）更高。我们的结论是，AMG和BNST提供传入输入的orexin含有神经元参与介导的心肺反应通过穹窿周围和背内侧下丘脑。

We previously showed that the defense response elicited by stressors was attenuated in prepro-orexin knockout mice and in orexin neuron-ablated mice, and we proposed that orexin serves as a master switch within multiple efferent pathways that mediate the defense response. In this study we sought to determine whether excitation of the amygdala (AMG) or the bed nucleus of stria terminalis (BNST) activates orexin-containing neurons and whether those neurons are essential in eliciting cardiorespiratory responses to the stimulus. In urethane-anesthetized mice, the GABA-A receptor antagonist bicuculline was microinjected into the AMG or BNST at sites where electrical stimulation induced simultaneous increases in blood pressure, heart rate, respiratory frequency, and tidal volume. Injection of bicuculline in either site induced long-lasting dose-dependent cardiorespiratory excitation in wild-type mice. In contrast, mice in which orexin neurons had been ablated demonstrated no such response after activation of the AMG and only a small response after activation of the BNST. Double immunohistochemical staining for orexin and c-Fos, an indicator of neural activation, revealed that an injection of bicuculline induced significantly larger numbers of orexin positive neurons that expressed c-Fos in the medial portion of the hypothalamus (58.2 ± 6.4 % into AMG and 66.4 ± 6.6 % into BNST, n=3 each) than did vehicle (18.2 ± 4.4 % into AMG and 28.3 ± 2.1 % into BNST). We conclude that the AMG and the BNST provide afferent input to the orexin-containing neurons that are involved in mediating the cardiorespiratory responses through the perifornical and dorsomedial hypothalamus.