Swiss Federal Institute of Technology (ETH), Zurich 8092, Switzerland.
Proc Biol Sci. 2011 Jun 22;278(1713):1864-72. doi: 10.1098/rspb.2010.2040. Epub 2010 Nov 24.
Immune-to-brain communication is essential for an individual to aptly respond to challenging internal and external environments. However, the specificity by which the central nervous system detects or 'senses' peripheral immune challenges is still poorly understood. In contrast to post-mortem c-Fos mapping, we recorded neural activity in vivo in two specific cortico-limbic regions relevant for processing visceral inputs and associating it with other sensory signalling, the amygdala (Am) and the insular cortex (IC). Adult rats were implanted with deep-brain monopolar electrodes and electrical activity was monitored unilaterally before and after administration of two different immunogens, the T-cell-independent antigen lipopolysaccharide (LPS) or the T-cell-dependent antigen staphylococcal enterotoxin B (SEB). In addition, the neural activity of the same individuals was analysed after single as well as repeated antigen administration, the latter inducing attenuation of the immune response. Body temperature and circulating cytokine levels confirmed the biological activity of the antigens and the success of immunization and desensitization protocols. More importantly, the present data demonstrate that neural activity of the Am and IC is not only specific for the type of immune challenge (LPS versus SEB) but seems to be also sensitive to the different immune state (naive versus desensitization). This indicates that the forebrain expresses specific patterns of electrical activity related to the type of peripheral immune activation as well as to the intensity of the stimulation, substantiating associative learning paradigms employing antigens as unconditioned stimuli. Overall, our data support the view of an intensive immune-to-brain communication, which may have evolved to achieve the complex energetic balance necessary for mounting effective immunity and improved individual adaptability by cognitive functions.
免疫-脑通讯对于个体对外界和内部环境的挑战做出适当反应至关重要。然而,中枢神经系统检测或“感知”外周免疫挑战的特异性仍知之甚少。与死后 c-Fos 映射相反,我们记录了两个与处理内脏输入和将其与其他感觉信号相关的特定皮质-边缘区域(杏仁核和岛叶皮质)的体内神经活动。成年大鼠被植入深部脑单极电极,在给予两种不同免疫原(T 细胞非依赖性抗原脂多糖[LPS]或 T 细胞依赖性抗原葡萄球菌肠毒素 B [SEB])之前和之后,对其单侧的神经活动进行监测。此外,我们还分析了相同个体在单次和重复抗原给药后的神经活动,后者会导致免疫反应减弱。体温和循环细胞因子水平证实了抗原的生物学活性以及免疫和脱敏方案的成功。更重要的是,本数据表明,杏仁核和岛叶皮质的神经活动不仅对免疫挑战的类型(LPS 与 SEB)具有特异性,而且似乎对不同的免疫状态(未致敏与脱敏)也敏感。这表明前脑表达与外周免疫激活类型以及刺激强度相关的特定电活动模式,证实了将抗原作为非条件刺激应用于联想学习范式。总的来说,我们的数据支持免疫-脑通讯密集的观点,这可能是为了实现复杂的能量平衡而进化而来的,这种能量平衡对于产生有效的免疫反应和通过认知功能提高个体适应性是必要的。