Zuperku Edward J, Stucke Astrid G, Hopp Francis A, Stuth Eckehard A E
Clement J. Zablocki Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin;
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
J Neurophysiol. 2017 Mar 1;117(3):1030-1042. doi: 10.1152/jn.00591.2016. Epub 2016 Dec 14.
The role of the dorsolateral pons in the control of expiratory duration (Te) and breathing frequency is incompletely understood. A subregion of the pontine parabrachial-Kölliker-Fuse (PB-KF) complex of dogs was identified via microinjections, in which localized pharmacologically induced increases in neuronal activity produced increases in breathing rate while decreases in neuronal activity produced decreases in breathing rate. This subregion is also very sensitive to local and systemic opioids. The purpose of this study was to precisely characterize the relationship between the PB-KF subregion pattern of altered neuronal activity and the control of respiratory phase timing as well as the time course of the phrenic nerve activity/neurogram (PNG). Pulse train electrical stimulation patterns synchronized with the onset of the expiratory (E) and/or phrenic inspiratory (I) phase were delivered via a small concentric bipolar electrode while the PNG was recorded in decerebrate, vagotomized dogs. Step frequency patterns during the E phase produced a marked frequency-dependent decrease in Te, while similar step inputs during the I phase increased inspiratory duration (Ti) by 14 ± 3%. Delayed pulse trains were capable of pacing the breathing rate by terminating the E phase and also of triggering a consistent stereotypical inspiratory PNG pattern, even when evoked during apnea. This property suggests that the I-phase pattern generator functions in a monostable circuit mode with a stable E phase and a transient I phase. Thus the I-pattern generator must contain neurons with nonlinear pacemaker-like properties, which allow the network to rapidly obtain a full on-state followed by relatively slow inactivation. The activated network can be further modulated and supplies excitatory drive to the neurons involved with pattern generation. A circumscribed subregion of the pontine medial parabrachial nucleus plays a key role in the control of breathing frequency primarily via changes in expiratory duration. Excitation of this subregion triggers the onset of the inspiratory phase, resulting in a stereotypical ramplike phrenic activity pattern independent of time within the expiratory phase. The ability to pace the I-burst rate suggests that the in vivo I-pattern generating network must contain functioning pacemaker neurons.
脑桥背外侧在呼气时长（Te）和呼吸频率控制中的作用尚未完全明了。通过微注射确定了犬脑桥臂旁-柯利克-福斯（PB-KF）复合体的一个亚区域，局部药理学诱导的神经元活动增加会使呼吸频率升高，而神经元活动减少则会使呼吸频率降低。该亚区域对局部和全身阿片类药物也非常敏感。本研究的目的是精确描述PB-KF亚区域神经元活动改变模式与呼吸相定时控制以及膈神经活动/神经图（PNG）时间进程之间的关系。在去大脑、切断迷走神经的犬中记录PNG时，通过一个小型同心双极电极传递与呼气（E）和/或膈神经吸气（I）相起始同步的脉冲串电刺激模式。E相期间的阶梯频率模式使Te产生明显的频率依赖性降低，而I相期间类似的阶梯输入使吸气时长（Ti）增加了14±3%。延迟脉冲串能够通过终止E相来调节呼吸频率，并且即使在呼吸暂停期间诱发，也能触发一致的刻板吸气PNG模式。这一特性表明I相模式发生器以单稳态电路模式运行，具有稳定的E相和短暂的I相。因此，I模式发生器必须包含具有非线性起搏器样特性的神经元，这使得网络能够迅速达到完全开启状态，随后相对缓慢地失活。被激活的网络可以进一步被调节，并为参与模式生成的神经元提供兴奋性驱动。脑桥内侧臂旁核的一个限定亚区域在呼吸频率控制中主要通过呼气时长的变化起关键作用。该亚区域的兴奋触发吸气相的起始，导致一种与呼气相内时间无关的刻板斜坡样膈神经活动模式。调节I爆发频率的能力表明，体内I模式生成网络必须包含功能正常的起搏器神经元。
