Li H Y, Sawchenko P E
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, and The Foundation for Medical Research, La Jolla, California 92037, USA.
J Comp Neurol. 1998 Apr 6;393(2):244-66.
Immunolocalization of Fos protein was used to identify and characterize hypothalamic visceromotor populations responsive to acute and chronic intermittent footshock stress, and candidate afferent mediators of hypothalamic effects. Exposure to a single 30 minute footshock session induced maximal Fos expression in the paraventricular hypothalamic nucleus (PVH) 2 hours after the challenge; activated cells corresponded principally to hypophysiotropic neurons expressing corticotropin-releasing factor, with secondary involvement of magnocellular oxytocinergic and autonomic-related projection neurons. Extrahypothalamic cell groups activated in response to acute footshock included ones associated with the processing or modulation of somatosensory/nociceptive inputs, the limbic region of the telencephalon, and visceral sensory mechanisms. Rats with constant corticosterone levels displayed enhanced footshock-induced Fos expression in the parvicellular compartment of the PVH, as well as in certain limbic and somatosensory cell groups, the locus coeruleus, but not in medullary catecholaminergic cell groups. Animals subjected to chronic intermittent stress (2 sessions/day for 7 days) showed only modest evidence of habituation of cellular activation responses in the PVH and most extrahypothalamic regions. Rats bearing retrograde tracer deposits in the PVH and killed 2 hours after acute footshock displayed Fos-positive retrogradely labeled neurons principally in medullary catecholaminergic cell groups, with secondary foci in the hypothalamus, limbic region, and pontine tegmentum. This characterization of footshock-responsive systems identifies cell groups that are in a position to (1) mediate acute stress effects on hypothalamic visceromotor neurons, (2) comprise targets for corticosteroid negative feedback effects, and/or (3) underlie habituation of the neuroendocrine limb of the stress response.
采用Fos蛋白免疫定位法来识别和表征对急性和慢性间歇性足部电击应激产生反应的下丘脑内脏运动神经元群，以及下丘脑效应的候选传入介质。暴露于单次30分钟的足部电击刺激后，在刺激后2小时，室旁下丘脑核（PVH）中诱导出最大的Fos表达；激活的细胞主要对应于表达促肾上腺皮质激素释放因子的促垂体神经元，大细胞催产素能和自主神经相关投射神经元也有次要参与。对急性足部电击产生反应而激活的下丘脑外细胞群包括与体感/伤害性输入的处理或调节、端脑边缘区域以及内脏感觉机制相关的细胞群。皮质酮水平恒定的大鼠在PVH的小细胞区以及某些边缘和体感细胞群、蓝斑中，足部电击诱导的Fos表达增强，但在髓质儿茶酚胺能细胞群中未增强。接受慢性间歇性应激（每天2次，共7天）的动物在PVH和大多数下丘脑外区域仅表现出细胞激活反应适度的习惯化证据。在PVH中植入逆行示踪剂沉积物并在急性足部电击后2小时处死的大鼠，Fos阳性逆行标记神经元主要在髓质儿茶酚胺能细胞群中，在下丘脑、边缘区域和脑桥被盖中有次要焦点。这种对足部电击反应系统的表征确定了能够（1）介导急性应激对下丘脑内脏运动神经元的影响、（2）构成皮质类固醇负反馈作用的靶点和/或（3）作为应激反应神经内分泌分支习惯化基础的细胞群。
