Correlation between cellular expression of transcription factors and of phosphorylated glutamate receptors under conditioned fear stress

我们研究了条件恐惧应激（CF）作为应激操作对前额皮质（PFC）、扣带皮质（Cg）、伏隔核（NAC）、杏仁核（AMY）、腹侧被盖区（VTA）、黑质（SN）、中缝背核（DR）和蓝斑（LC）单胺能、y -氨基丁酸（GABA）能和谷氨酸能细胞中Fos表达的影响。采用双标记技术，将Fos免疫染色与酪氨酸羟化酶（TH）、5-羟色胺（5-HT）或GABA免疫染色相结合，对应激后活化神经元进行组织化学鉴定。足部休克（FS）和CF应激后，PFC、背侧DR和LC等许多区域的fos阳性细胞数量均显著增加，而NAC、AMY、VTA和SN的fos阳性细胞数量未增加。CF组PFC、DR、LC中fos样免疫反应性均低于FS组相应值。LC中60%的fos阳性细胞与TH或GABA共定位。同样，DR中的许多fos阳性细胞与5-HT或GABA.3共定位。PFC、PVN、DR、LC中50%的fos阳性细胞与谷氨酸n -甲基- d -天冬氨酸（NMDA）受体亚基1（NR-1）共定位。在FS和CF胁迫下，PFC、PVN、SN、DR、LC中磷酸化谷氨酸受体亚基的蛋白没有变化。这些结果表明，CF可诱导去甲肾上腺素能和血清素能神经元中Fos的强烈表达，而多巴胺能神经元中Fos的表达不明显，并且这些核中的gaba能和谷氨酸能神经元通常被应激激活。

we examined the effects of conditioned fear stress(CF) as a stressful manipulation on Fos expression in both monoaminergic, Y-aminobutyric acid(GABA)-ergic and glutamatergic cells in the the prefrontal cortex(PFC), cingulate cortex(Cg), nucleus accumbens(NAC), amygdala(AMY), ventral tegmental area(VTA), substantia nigra(SN) dorsal raphe nucleus(DR), and locus coeruleus(LC). With a double-labeling technique, Fos immunostaining was combined with that for tyrosine hydroxylase(TH), serotonin (5-HT) or GABA for histochemical identification of activated neurons following the stress.1.Following both the foot shock(FS) and CF stress, the number of Fos-positive cells significantly increased in many regions including the PFC, dorsal DR, and LC whereas did not increase in NAC, AMY, VTA,and SN. In the CF group, Fos-like immunoreactivity was lower in PFC,DR, or LC than corresponding value in the FS group.2.Sixty percentages of Fos-positive cells in the LC were colocalized with either TH or GABA. Similarly, many of Fos-positive cells in the DR were colocalized with either 5-HT or GABA.3.Forty-Fifty percentages of Fos-positive cells in the PFC, PVN, DR, LC were colocalized with glutamate N-methyl-D-aspartate(NMDA) receptor subunit 1(NR-1).4.Following both the FS and CF stress, Protein of the phosphorylated glutamate receptor subunits did not change in the PFC, PVN, SN, DR, LC.These results indicate that the CF could induce intense Fos expression in the noradrenergic and serotonergic neurons, but not in the dopaminergic neurons, and that GABAergic and glutamatergic neurons in these nuclei are commonly activated by the stress.