Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, United States.
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, United States.
Elife. 2023 Jun 5;12:e86103. doi: 10.7554/eLife.86103.
Breathing needs to be tightly coordinated with upper airway behaviors, such as swallowing. Discoordination leads to aspiration pneumonia, the leading cause of death in neurodegenerative disease. Here, we study the role of the postinspiratory complex (PiCo) in coordinating breathing and swallowing. Using optogenetic approaches in freely breathing anesthetized ChATcre:Ai32, Vglut2cre:Ai32 and intersectional recombination of ChATcre:Vglut2FlpO:ChR2 mice reveals PiCo mediates airway protective behaviors. Activation of PiCo during inspiration or the beginning of postinspiration triggers swallow behavior in an all-or-nothing manner, while there is a higher probability for stimulating only laryngeal activation when activated further into expiration. Laryngeal activation is dependent on stimulation duration. Sufficient bilateral PiCo activation is necessary for preserving the physiological swallow motor sequence since activation of only a few PiCo neurons or unilateral activation leads to blurred upper airway behavioral responses. We believe PiCo acts as an interface between the swallow pattern generator and the preBötzinger complex to coordinate swallow and breathing. Investigating PiCo's role in swallow and laryngeal coordination will aid in understanding discoordination with breathing in neurological diseases.
呼吸需要与上呼吸道行为(如吞咽)紧密协调。不协调会导致吸入性肺炎,这是神经退行性疾病死亡的主要原因。在这里,我们研究了后吸气复合(PiCo)在协调呼吸和吞咽中的作用。在自由呼吸麻醉的 ChATcre:Ai32、Vglut2cre:Ai32 和 ChATcre:Vglut2FlpO:ChR2 小鼠的交叉重组中,使用光遗传学方法揭示 PiCo 介导气道保护行为。在吸气或后吸气开始时激活 PiCo 会以全有或全无的方式触发吞咽行为,而在呼气进一步进入时,刺激仅引起喉激活的可能性更高。喉激活依赖于刺激持续时间。只有少数几个 PiCo 神经元或单侧激活足以保持生理吞咽运动序列,因为只有充分激活双侧 PiCo 才能保留生理吞咽运动序列,导致上呼吸道行为反应模糊。我们认为 PiCo 作为吞咽模式发生器和前 Bötzinger 复合体之间的接口,协调吞咽和呼吸。研究 PiCo 在吞咽和喉协调中的作用将有助于理解神经疾病中呼吸不协调的原因。