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Central Neural Mechanisms of the Defense Response against Stressor

针对压力源的防御反应的中枢神经机制

基本信息

批准号：
18590203
负责人：
KUWAKI Tomoyuki
金额：
$ 2.5万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590203/
关键词：
Defense Response Stress Hypothalamus Amygdala Orexin Transgenic Mouse Bed Nucleus of the Stria Terminalis

项目摘要

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.

我们先前的研究表明，在原增食欲素基因敲除小鼠和食欲素神经元消融小鼠中，应激源引起的防御反应被减弱，我们认为增食欲素在调节防御反应的多个传出通路中起着主开关的作用。在这项研究中，我们试图确定兴奋杏仁核(AMG)或终纹床核(BNST)是否激活了含有食欲素的神经元，以及这些神经元是否在诱发对刺激的心肺反应中起关键作用。在乌拉坦麻醉的小鼠中，在电刺激引起血压、心率、呼吸频率和潮气量同时增加的部位，将GABA-A受体拮抗剂荷包牡丹碱微量注射到AMG或BNST。荷包牡丹碱在任一部位均可诱导野生型小鼠长时间的心肺兴奋，呈剂量依赖性。相比之下，去掉食欲素神经元的小鼠在激活AMG后没有表现出这样的反应，而在激活BNST后只有很小的反应。免疫组织化学双重染色显示，注射荷包牡丹碱后，下丘脑内侧部表达c-Fos的增食欲素阳性神经元数量(AMG为58.2±6.4%，BNST为66.4±6.6%，n=3)明显多于安慰剂组(AMG为18.2±4.4%，BNST为28.3±2.1%)。我们的结论是，AMG和BNST通过穹隆周围和背内侧下丘脑为参与介导心肺反应的食欲素神经元提供传入输入。