Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California 90095-1763, USA.
J Neurosci. 2013 May 29;33(22):9235-45. doi: 10.1523/JNEUROSCI.4143-12.2013.
In the mammalian respiratory central pattern generator, the preBötzinger complex (preBötC) produces rhythmic bursts that drive inspiratory motor output. Cellular mechanisms initiated by each burst are hypothesized to be necessary to determine the timing of the subsequent burst, playing a critical role in rhythmogenesis. To explore mechanisms relating inspiratory burst generation to rhythmogenesis, we compared preBötC and hypoglossal (XII) nerve motor activity in medullary slices from neonatal mice in conditions where periods between successive inspiratory XII bursts were highly variable and distributed multimodally. This pattern resulted from rhythmic preBötC neural population activity that consisted of bursts, concurrent with XII bursts, intermingled with significantly smaller "burstlets". Burstlets occurred at regular intervals during significantly longer XII interburst intervals, at times when a XII burst was expected. When a preBötC burst occurred, its high amplitude inspiratory component (I-burst) was preceded by a preinspiratory component that closely resembled the rising phase of burstlets. Cadmium (8 μM) eliminated preBötC and XII bursts, but rhythmic preBötC burstlets persisted. Burstlets and preinspiratory activity were observed in ~90% of preBötC neurons that were active during I-bursts. When preBötC excitability was raised significantly, burstlets could leak through to motor output in medullary slices and in vivo in adult anesthetized rats. Thus, rhythmic bursting, a fundamental mode of nervous system activity and an essential element of breathing, can be deconstructed into a rhythmogenic process producing low amplitude burstlets and preinspiratory activity that determine timing, and a pattern-generating process producing suprathreshold I-bursts essential for motor output.
在哺乳动物呼吸中枢模式发生器中，前脑桥呼吸组（preBötC）产生节律性爆发，驱动吸气运动输出。每个爆发引发的细胞机制被假设为确定随后爆发时间的必要条件，在节律发生中起着关键作用。为了探索与吸气爆发产生相关的节律发生机制，我们比较了新生小鼠延髓切片中 preBötC 和舌下神经（XII）神经运动活动，在这些条件下，连续吸气 XII 爆发之间的周期高度可变且呈多峰分布。这种模式是由与 XII 爆发同时发生的、与 XII 爆发混合的、显著较小的“爆发子”的节律性 preBötC 神经群体活动引起的。爆发子在 XII 爆发之间显著较长的时间间隔内以规则的间隔发生，此时预计会发生 XII 爆发。当发生 preBötC 爆发时，其高振幅吸气成分（I-爆发）之前是类似于爆发子上升相的预吸气成分。镉（8 μM）消除了 preBötC 和 XII 爆发，但节律性 preBötC 爆发子持续存在。在 I-爆发期间活跃的大约 90%的 preBötC 神经元中观察到爆发子和预吸气活动。当 preBötC 兴奋性显著升高时，爆发子可以在延髓切片和麻醉成年大鼠体内的运动输出中泄漏。因此，节律性爆发是神经系统活动的基本模式，也是呼吸的必要组成部分，可以分解为产生低振幅爆发子和预吸气活动的节律发生过程，该过程确定时间，并产生产生对运动输出至关重要的超阈值 I-爆发的模式发生过程。
