Asymmetric control of inspiratory and expiratory phases by excitability in the respiratory network of neonatal mice in vitro
Asymmetric control of inspiratory and expiratory phases by excitability in the respiratory network of neonatal mice in vitro
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DOI：
10.1113/jphysiol.2008.164079
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发表时间：
2009-03-15
影响因子：
5.5
通讯作者：
Feldman, Jack L.
中科院分区：
文献类型：
--
作者：
Del Negro, Christopher A.;Kam, Kaiwen;Feldman, Jack L.
节律性运动行为包括交替运动，例如踏步时的摇摆姿势、咀嚼时的下巴张开和闭合以及呼吸时的吸气呼气，这些运动的频率必须不稳定，并且在某些情况下，在各个阶段的持续时间内必须不稳定，以适应生理需求。这些运动是潜在神经回路的表达，其组织控制着运动行为的性质。为了确定在呼吸中在宽频率范围内操作的能力是否在节律发生器中表达，我们使用来自新生小鼠的节律活性体外切片分离基本呼吸回路的核心。我们在这些切片中显示呼吸运动输出在非常低的频率（0.008 Hz），远低于典型的频率在体外（类似于0.2 Hz），在大多数完整的正常体温的哺乳动物。在这个广泛的频率范围内，吸气运动输出爆发在模式上保持显著恒定，即持续时间、峰值幅度和面积。频率的变化，而不是归因于增加的爆发间隔，并在很大程度上不受快速抑制传输的删除。频率的调制主要通过操纵细胞外钾来实现，这显著影响神经元的兴奋性。当兴奋性降低，以减缓，或在某些情况下停止，自发节律，呼吸网络的短暂刺激与一个martamatergic激动剂可以唤起（节奏）运动输出。在慢（< 0.02 Hz）自发节律的切片中，诱发运动输出可以在短（60 s）的自发爆发之后。我们观察到在吸气期间由Na+/K+ ATP酶产生的大幅度（类似于0.6 nA）外向电流，其在25-100 ms内失活，因此可能有助于猝发终止和诱发猝发的潜伏期，但不太可能控制猝发间期。我们认为，呼吸网络的功能在很宽的频率范围内，通过从事不同的机制，从那些控制吸气持续时间和模式，具体管理的爆发间隔。
Rhythmic motor behaviours consist of alternating movements, e.g. swing-stance in stepping, jaw opening and closing during chewing, and inspiration-expiration in breathing, which must be labile in frequency, and in some cases, in the duration of individual phases, to adjust to physiological demands. These movements are the expression of underlying neural circuits whose organization governs the properties of the motor behaviour. To determine if the ability to operate over a broad range of frequencies in respiration is expressed in the rhythm generator, we isolated the kernel of essential respiratory circuits using rhythmically active in vitro slices from neonatal mice. We show respiratory motor output in these slices at very low frequencies (0.008 Hz), well below the typical frequency in vitro (similar to 0.2 Hz) and in most intact normothermic mammals. Across this broad range of frequencies, inspiratory motor output bursts remained remarkably constant in pattern, i.e. duration, peak amplitude and area. The change in frequency was instead attributable to increased interburst interval, and was largely unaffected by removal of fast inhibitory transmission. Modulation of the frequency was primarily achieved by manipulating extracellular potassium, which significantly affects neuronal excitability. When excitability was lowered to slow down, or in some cases stop, spontaneous rhythm, brief stimulation of the respiratory network with a glutamatergic agonist could evoke (rhythmic) motor output. In slices with slow (< 0.02 Hz) spontaneous rhythms, evoked motor output could follow a spontaneous burst at short ( 60 s. We observed during inspiration a large magnitude (similar to 0.6 nA) outward current generated by Na+/K+ ATPase that deactivated in 25-100 ms and thus could contribute to burst termination and the latency of evoked bursts but is unlikely to control the interburst interval. We propose that the respiratory network functions over a broad range of frequencies by engaging distinct mechanisms from those controlling inspiratory duration and pattern that specifically govern the interburst interval.