The pre-Bötzinger complex is necessary for the expression of post-inspiration

Abstract

The mammalian three-phase respiratory motor pattern of inspiration, post-inspiration and expiration is expressed in spinal and cranial motor nerve activities. This pattern is generated by a hierarchical brainstem-wide pre-motor network. However, the local rhythmogenic circuit of the pre-Botzinger complex (pre-BotC) was established as the noeud vitale necessary and sufficient to initiate inspiration. In present study, we tested the effect of unilateral and bilateral inactivation of the pre-BotC (microinjection of the GABAA receptor agonist isoguvacine 10 mM, 50 nl) on respiratory motor activities in an in situ perfused brainstem preparation of rat. As expected, bilateral inactivation of the pre-BotC triggered cessation of phrenic (PNA), hypoglossal (HNA) and vagal (VNA) nerve activities for 15-20 min. Partial recovery from bilateral isoguvacine injection was characterized by erratic activity in all recorded motor nerves reminiscent to patterns observed after disturbed excitatory-inhibitory balance within the local pre-BotC circuit. Surprisingly, ipsilateral isoguvacine injections into the pre-BotC triggered transient (6-8 min) cessation of inspiratory and post-inspiratory VNA (p<0.001) and suppressed inspiratory HNA by -70 {+/-} 15% (p<0.01), while inspiratory PNA burst frequency increased by 46 {+/-} 30% (p<0.01). Taken together, these observations confirm the role of the pre-BotC as the noeud vitale of the mammalian respiratory network in situ and highlight a significant role for the pre-BotC in the expression of vagal post-inspiratory and inspiratory activity.