Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis

被引:59
作者
Wittmeier, Steffen [1 ]
Song, Gang [1 ]
Duffin, James [2 ,3 ]
Poon, Chi-Sang [1 ]
机构
[1] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[2] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Dept Anaesthesia, Toronto, ON M5S 1A8, Canada
基金
美国国家卫生研究院;
关键词
entrainment; parafacial respiratory group; postinhibitory rebound; preBotzinger complex; rhythm;
D O I
10.1073/pnas.0809377105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Inspiratory and expiratory rhythms in mammals are thought to be generated by pacemaker-like neurons in 2 discrete brainstem regions:. pre-Botzinger complex (preBotC) and parafacial respiratory group (pFRG). How these putative pacemakers or pacemaker networks may interact to set the overall respiratory rhythm in synchrony remains unclear. Here, we show that a pacemakers 2-way "handshake" process comprising pFRG excitation of the preBotC, followed by reverse inhibition and postinhibitory rebound (PIR) excitation of the pFRG and postinspiratory feedback inhibition of the preBotC, can provide a phase-locked mechanism that sequentially resets and, hence, synchronizes the inspiratory and expiratory rhythms in neonates. The order of this handshake sequence and its progression vary depending on the relative excitabilities of the preBotC vs. the pFRG and resultant modulations of the PIR in various excited and depressed states, leading to complex inspiratory and expiratory phase-resetting behaviors in neonates and adults. This parsimonious model of pacemakers synchronization and mutual entrainment replicates key experimental data in vitro and in vivo that delineate the developmental changes in respiratory rhythm from neonates to maturity, elucidating their underlying mechanisms and suggesting hypotheses for further experimental testing. Such a pacemakers handshake process with conjugate excitation-inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals.
引用
收藏
页码:18000 / 18005
页数:6
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