Passerin A M, Cano G, Rabin B S, Delano B A, Napier J L, Sved A F
Departments of Neuroscience, University of Pittsburgh, PA 15260, USA.
Neuroscience. 2000;101(4):1071-82. doi: 10.1016/s0306-4522(00)00372-9.
The robust activation of locus coeruleus neurons in response to a variety of stressors, in conjunction with the widespread outputs of the locus coeruleus, suggest that the locus coeruleus may be important in mediating responses to stress. Previous studies in rats have demonstrated that exposure to foot shock elicits Fos expression, a marker of neuronal activation, in the locus coeruleus and other brain sites. In order to evaluate the involvement of the locus coeruleus in foot shock-induced activation of other brain sites, shock-induced Fos expression was examined in the locus coeruleus and other brain areas known to be activated by foot shock, following direct inhibition of the locus coeruleus by local infusion of muscimol, a GABA agonist, prior to foot shock. Control rats received infusions of artificial cerebrospinal fluid into the locus coeruleus or muscimol into areas outside of locus coeruleus. Rats infused with artificial cerebrospinal fluid and then exposed to foot shock had significant increases in Fos expression in several brain areas, including locus coeruleus, nucleus O, several subdivisions of the hypothalamus, subnuclei of amygdala, bed nucleus of the stria terminalis and cingulate cortex. Inhibition of the locus coeruleus prior to foot shock significantly inhibited Fos expression in the locus coeruleus, nucleus O, some subdivisions of the hypothalamus including the magnocellular and medial parvicellular paraventricular hypothalamic nucleus, subnuclei of amygdala, and cingulate cortex. In contrast, inhibition of the locus coeruleus did not affect shock-induced Fos expression in other areas, including certain subdivisions of the hypothalamus and bed nucleus of the stria terminalis. We suggest that foot shock may activate multiple pathways, with activation of certain discrete nuclei requiring input from the locus coeruleus and activation of others occurring independently of locus coeruleus input.
蓝斑神经元对多种应激源产生强烈激活，再加上蓝斑广泛的投射，这表明蓝斑在介导应激反应中可能起重要作用。先前对大鼠的研究表明，足部电击会引发蓝斑及其他脑区中Fos表达，Fos是神经元激活的标志物。为了评估蓝斑在足部电击诱导的其他脑区激活中的作用，在足部电击前通过局部注入GABA激动剂蝇蕈醇直接抑制蓝斑后，检测蓝斑及其他已知会被足部电击激活的脑区中电击诱导的Fos表达。对照大鼠向蓝斑注入人工脑脊液，或向蓝斑以外区域注入蝇蕈醇。注入人工脑脊液后再接受足部电击的大鼠，包括蓝斑、O核、下丘脑的几个亚区、杏仁核亚核、终纹床核和扣带回皮质在内的几个脑区中Fos表达显著增加。足部电击前抑制蓝斑可显著抑制蓝斑、O核、下丘脑的一些亚区（包括大细胞和内侧小细胞室旁下丘脑核）、杏仁核亚核和扣带回皮质中的Fos表达。相比之下，抑制蓝斑并不影响其他区域（包括下丘脑的某些亚区和终纹床核）中电击诱导的Fos表达。我们认为足部电击可能激活多条通路，某些离散核团的激活需要来自蓝斑的输入，而其他核团的激活则独立于蓝斑输入发生。
