Cinelli Elenia, Mutolo Donatella, Robertson Brita, Grillner Sten, Contini Massimo, Pantaleo Tito, Bongianni Fulvia
Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Viale G.B. Morgagni 63, 50134 Firenze, Italy.
J Physiol. 2014 Apr 15;592(8):1823-38. doi: 10.1113/jphysiol.2013.268086. Epub 2014 Feb 3.
We have previously shown that GABA and glycine modulate respiratory activity in the in vitro brainstem preparations of the lamprey and that blockade of GABAA and glycine receptors restores the respiratory rhythm during apnoea caused by blockade of ionotropic glutamate receptors. However, the neural substrates involved in these effects are unknown. To address this issue, the role of GABAA, GABAB and glycine receptors within the paratrigeminal respiratory group (pTRG), the proposed respiratory central pattern generator, and the vagal motoneuron region was investigated both during apnoea induced by blockade of glutamatergic transmission and under basal conditions through microinjections of specific antagonists. The removal of GABAergic, but not glycinergic transmission within the pTRG, causes the resumption of rhythmic respiratory activity during apnoea, and reveals the presence of a modulatory control of the pTRG under basal conditions. A blockade of GABAA and glycine receptors within the vagal region strongly increases the respiratory frequency through disinhibition of neurons projecting to the pTRG from the vagal region. These neurons were retrogradely labelled (neurobiotin) from the pTRG. Intense GABA immunoreactivity is observed both within the pTRG and the vagal area, which corroborates present findings. The results confirm the pTRG as a primary site of respiratory rhythm generation, and suggest that inhibition modulates the activity of rhythm-generating neurons, without any direct role in burst formation and termination mechanisms.
我们之前已经表明，γ-氨基丁酸（GABA）和甘氨酸可调节七鳃鳗体外脑干制剂中的呼吸活动，并且在离子型谷氨酸受体阻断引起的呼吸暂停期间，GABAA和甘氨酸受体的阻断可恢复呼吸节律。然而，参与这些效应的神经底物尚不清楚。为了解决这个问题，我们通过微量注射特异性拮抗剂，研究了三叉旁呼吸组（pTRG，即拟议的呼吸中枢模式发生器）和迷走运动神经元区域内GABAA、GABAB和甘氨酸受体在谷氨酸能传递阻断诱导的呼吸暂停期间以及基础条件下的作用。去除pTRG内的GABA能传递而非甘氨酸能传递，会导致呼吸暂停期间有节律的呼吸活动恢复，并揭示了基础条件下pTRG存在调节性控制。迷走神经区域内GABAA和甘氨酸受体的阻断通过解除对从迷走神经区域投射到pTRG的神经元的抑制，强烈增加呼吸频率。这些神经元是从pTRG逆行标记（神经生物素）的。在pTRG和迷走神经区域内均观察到强烈的GABA免疫反应性，这证实了目前的研究结果。结果证实pTRG是呼吸节律产生的主要部位，并表明抑制作用调节节律产生神经元的活动，而在爆发形成和终止机制中没有任何直接作用。
