Brambilla D, Franciosi S, Opp M R, Imeri L
Institute of Human Physiology II, Guiseppe Moruzzi Center for Experimental Sleep Research, University of Milan Medical School, Via Mangiagalli, 32, 20133 Milano, Italy.
Eur J Neurosci. 2007 Oct;26(7):1862-9. doi: 10.1111/j.1460-9568.2007.05796.x. Epub 2007 Sep 14.
In vitro electrophysiological data suggest that interleukin-1 may promote non-rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN). Interleukin-1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin-1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin-1beta. Coronal slices containing DRN were obtained from male Sprague-Dawley rats. The impact of interleukin-1 on firing rate and on evoked post-synaptic potentials was determined. Evoked post-synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin-1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 +/- 0.2 Hz (before administration) to 0.7 +/- 0.2 Hz. Electrical stimulation induced depolarizing evoked post-synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post-synaptic potential components: a GABAergic evoked inhibitory post-synaptic potentials and a glutamatergic evoked excitatory post-synaptic potentials, respectively. Interleukin-1 increased GABAergic evoked inhibitory post-synaptic potentials amplitudes by 30.3 +/- 3.8% (n = 6) without affecting glutamatergic evoked excitatory post-synaptic potentials. These results support the hypothesis that interleukin-1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin-1-induced potentiation of evoked GABAergic inhibitory responses.
体外电生理数据表明，白细胞介素-1可能通过抑制中缝背核（DRN）中觉醒活跃的5-羟色胺能神经元的自发放电来促进非快速眼动睡眠。白细胞介素-1增强GABA的抑制作用。DRN神经元受GABA能抑制性控制。本研究旨在验证白细胞介素-1通过增强GABA能抑制作用来抑制DRN 5-羟色胺能神经元的假说。进行体外细胞内记录以评估生理和药理学鉴定的DRN 5-羟色胺能神经元对大鼠重组白细胞介素-1β的反应。从雄性Sprague-Dawley大鼠获取含有DRN的冠状切片。确定白细胞介素-1对放电频率和诱发的突触后电位的影响。通过放置在DRN腹外侧切片表面的双极电极刺激诱发突触后电位。向灌流液中添加白细胞介素-1（25 ng/mL）可使DRN 5-羟色胺能神经元的放电频率从1.3±0.2 Hz（给药前）显著降低至0.7±0.2 Hz。电刺激在DRN 5-羟色胺能神经元中诱发去极化的突触后电位。应用谷氨酸能和GABA能拮抗剂揭示了两种不同的突触后电位成分：分别为GABA能诱发的抑制性突触后电位和谷氨酸能诱发的兴奋性突触后电位。白细胞介素-1使GABA能诱发的抑制性突触后电位幅度增加30.3±3.8%（n = 6），而不影响谷氨酸能诱发的兴奋性突触后电位。这些结果支持以下假说：白细胞介素-1对DRN 5-羟色胺能神经元的抑制作用是由白细胞介素-1诱导的诱发GABA能抑制反应增强介导。
