Inhibitory control of active expiration by the Bötzinger complex in rats.

Inhibitory control of active expiration by the Bötzinger complex in rats.
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DOI:
10.1113/jp280243
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发表时间:
2020-11
期刊:
The Journal of physiology
影响因子:
--
通讯作者:
Zoccal DB
Zoccal DB
中科院分区:
其他
文献类型:
--
作者:
Flor KC;Barnett WH;Karlen-Amarante M;Molkov YI;Zoccal DB

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Bötzinger 复合体 (BötC) 的呼气神经元为呼吸网络提供抑制性输入,在平静呼吸期间,呼吸网络对于呼吸相变和持续时间控制至关重要。在这里,我们研究了 BötC 神经元如何与位于面旁呼吸组 (pFRG) 的呼气振荡器相互作用,并在主动呼气期间控制腹部活动。使用幼年大鼠的去脑动脉原位灌注制剂,我们记录了呼气神经元的活动,并在高碳酸血症期间或暴露于短期持续缺氧(产生主动呼气的条件)后对 BötC 和 pFRG 进行药理学操作。将实验数据整合到数学模型中,以获得对呼吸中枢模式发生器内的抑制连接组的新见解。我们的结果表明,BötC 神经元可能与 pFRG 建立相互连接,在呼气第一阶段提供呼气抑制,并在呼气后期接收兴奋性输入。此外,我们发现在 BötC 中应用 GABA 能和甘氨酸能拮抗剂会对腹部呼气活动产生相反的影响,表明 BötC 内存在复杂的抑制回路。使用数学模型,我们提出 BötC 网络组织及其与 pFRG 的相互作用,以抑制静息条件下的腹部活动,并有助于在高碳酸血症期间或暴露于短期持续缺氧后观察到的主动呼气期间形成腹部呼气模式。
The expiratory neurons of the Bötzinger complex (BötC) provide inhibitory inputs to the respiratory network, which, during eupnea, are critically important for respiratory phase transition and duration control. Here, we investigated how the BötC neurons interact with the expiratory oscillator located in the parafacial respiratory group (pFRG) and control the abdominal activity during active expiration. Using the decerebrated, arterially perfused in situ preparations of juvenile rats, we recorded the activity of expiratory neurons and performed pharmacological manipulations of the BötC and pFRG during hypercapnia or after the exposure to short-term sustained hypoxia – conditions that generate active expiration. The experimental data were integrated in a mathematical model to gain new insights in the inhibitory connectome within the respiratory central pattern generator. Our results indicate that the BötC neurons may establish mutual connections with the pFRG, providing expiratory inhibition during the first stage of expiration and receiving excitatory inputs during late expiration. Moreover, we found that application of GABAergic and glycinergic antagonists in the BötC caused opposing effects on abdominal expiratory activity, suggesting complex inhibitory circuitry within the BötC. Using mathematical modeling, we propose the BötC network organization and its interactions with the pFRG to restrain abdominal activity under resting conditions and contribute to abdominal expiratory pattern formation during active expiration observed during hypercapnia or after the exposure to short-term sustained hypoxia.