Cinelli Elenia, Mutolo Donatella, Iovino Ludovica, Pantaleo Tito, Bongianni Fulvia
Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Firenze, Italy.
Eur J Neurosci. 2020 Oct;52(8):3903-3917. doi: 10.1111/ejn.14769. Epub 2020 May 26.
In mammals, 5-HTexcitatory respiratory effects imply 5-HT receptor-mediated disinhibition of pre-Bötzinger complex neurons. In the lamprey, 5-HT receptors are involved in the neural control of locomotion, but their role in the respiratory regulation, particularly at the level of the putative respiratory rhythm generator, the paratrigeminal respiratory group (pTRG), is not known. We here investigate the respiratory function of inhibitory 5-HT receptors within the pTRG of the isolated brainstem of the adult lamprey. The 5-HT receptor agonists either bath applied or microinjected into the pTRG did not cause significant effects. However, the selective 5-HT receptor antagonist (S)-WAY 100135 bath applied or microinjected into the pTRG induced depressing respiratory effects or even apnoea, thus revealing that 5-HT exerts a 5-HT receptor-mediated potent tonic influence on respiration and contributes to maintain baseline levels of respiratory activity. Microinjections of strychnine or bicuculline, either alone or in combination, into the pTRG prevented (S)-WAY 100135-induced apnoea. In addition, immunohistochemical studies corroborate the present findings suggesting that 5-HT receptors are widely expressed in close apposition to the soma of glycine-immunoreactive cells located within the pTRG region. The results show that in the lamprey respiratory network, 5-HT exerts a tonic influence on respiration by a potent inhibitory control on both GABAergic and glycinergic mechanisms. The observed disinhibitory effects resemble the excitatory respiratory modulation exerted by 5-HT receptor-mediated inhibition of glycinergic and/or GABAergic neurons present in mammals, supporting the notion that some features of the neuronal network subserving respiratory rhythm generation are highly conserved throughout phylogeny.
在哺乳动物中，5-羟色胺（5-HT）的兴奋性呼吸效应意味着5-HT受体介导的对前包钦格复合体神经元的去抑制作用。在七鳃鳗中，5-HT受体参与运动的神经控制，但其在呼吸调节中的作用，特别是在假定的呼吸节律发生器即三叉旁呼吸组（pTRG）水平上的作用尚不清楚。我们在此研究成年七鳃鳗离体脑干pTRG内抑制性5-HT受体的呼吸功能。将5-HT受体激动剂浴用或微量注射到pTRG中均未产生显著影响。然而，将选择性5-HT受体拮抗剂（S）-WAY 100135浴用或微量注射到pTRG中会诱发呼吸抑制效应甚至呼吸暂停，从而表明5-HT对呼吸施加5-HT受体介导的强大的紧张性影响，并有助于维持呼吸活动的基线水平。单独或联合向pTRG中微量注射士的宁或荷包牡丹碱可预防（S）-WAY 100135诱发的呼吸暂停。此外，免疫组织化学研究证实了目前的发现，提示5-HT受体广泛表达于与位于pTRG区域内的甘氨酸免疫反应性细胞的胞体紧密相邻处。结果表明，在七鳃鳗呼吸网络中，5-HT通过对GABA能和甘氨酸能机制的强大抑制性控制对呼吸施加紧张性影响。观察到的去抑制效应类似于哺乳动物中5-HT受体介导的对甘氨酸能和/或GABA能神经元的抑制所产生的兴奋性呼吸调节，支持了这样一种观点，即参与呼吸节律产生的神经网络的某些特征在整个系统发育过程中高度保守。
