Biological Sciences, University of Missouri, Columbia, MO 65211, USA.
J Exp Biol. 2023 Sep 15;226(18). doi: 10.1242/jeb.245951. Epub 2023 Sep 22.
Breathing is generated by a rhythmic neural circuit in the brainstem, which contains conserved elements across vertebrate groups. In adult frogs, the 'lung area' located in the reticularis parvocellularis is thought to represent the core rhythm generator for breathing. Although this region is necessary for breathing-related motor output, whether it functions as an endogenous oscillator when isolated from other brainstem centers is not clear. Therefore, we generated thick brainstem sections that encompass the lung area to determine whether it can generate breathing-related motor output in a highly reduced preparation. Brainstem sections did not produce activity. However, subsaturating block of glycine receptors reliably led to the emergence of rhythmic motor output that was further enhanced by blockade of GABAA receptors. Output occurred in singlets and multi-burst episodes resembling the intact network. However, burst frequency was slower and individual bursts had longer durations than those produced by the intact preparation. In addition, burst frequency was reduced by noradrenaline and μ-opioids, and increased by serotonin, as observed in the intact network and in vivo. These results suggest that the lung area can be activated to produce rhythmic respiratory-related motor output in a reduced brainstem section and provide new insights into respiratory rhythm generation in adult amphibians. First, clustering breaths into episodes can occur within the rhythm-generating network without long-range input from structures such as the pons. Second, local inhibition near, or within, the rhythmogenic center may need to be overridden to express the respiratory rhythm.
呼吸是由脑干中的节律性神经回路产生的，该回路包含脊椎动物群体中保守的元素。在成年青蛙中，位于网状小细胞区的“肺区”被认为是呼吸的核心节律发生器。尽管该区域对于与呼吸相关的运动输出是必需的，但当与脑干其他中心隔离时，它是否作为内源性振荡器发挥作用尚不清楚。因此，我们生成了包含肺区的厚脑干切片，以确定它是否可以在高度简化的制备中产生与呼吸相关的运动输出。脑干切片没有产生活动。然而，甘氨酸受体的亚饱和阻断可靠地导致节律性运动输出的出现，并且 GABA A 受体的阻断进一步增强了输出。输出发生在类似于完整网络的单脉冲和多爆发事件中。然而，与完整制剂产生的爆发相比，爆发频率较慢，单个爆发持续时间更长。此外，爆发频率被去甲肾上腺素和μ阿片类物质降低，而被 5-羟色胺增加，如在完整网络和体内观察到的那样。这些结果表明，肺区可以在简化的脑干切片中被激活以产生节律性呼吸相关的运动输出，并为成年两栖动物的呼吸节律产生提供新的见解。首先，在没有来自脑桥等结构的远程输入的情况下，呼吸可以聚类成爆发。其次，可能需要克服节律生成中心附近或中心内的局部抑制以表达呼吸节律。
