Optogenetic stimulation of pre-Bötzinger complex reveals novel circuit interactions in swallowing-breathing coordination.
Optogenetic stimulation of pre-Bötzinger complex reveals novel circuit interactions in swallowing-breathing coordination.
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DOI：
10.1073/pnas.2121095119
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发表时间：
2022-07-19
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
吞咽是一种必须与呼吸协调的重要行为。这两种行为都起源于延髓，但负责它们相互作用的途径尚未确定。据推测，来自延髓吸气驱动器的抑制，前BötC复合物（preBötC），抑制了吸气期间发生的吞咽。使用抑制性和兴奋性preBötC神经元的光遗传学刺激，我们提供了preBötC参与正常吞咽生产和呼吸协调的证据。我们还建议前BötC连接到疑核（NA）的喉运动神经元和Dbx 1神经元的模拟延迟喉关闭，破坏正常的吞咽序列。这项研究探讨了吞咽呼吸协调的神经通路。吞咽与呼吸的协调，特别是吸气，对于大多数生物体的稳态是必不可少的。虽然人们对哺乳动物中对灵感至关重要的神经元网络--前伯青格复合体（pre-BötC）--了解得很多，但对这个网络如何与吞咽相互作用知之甚少。在这里，我们激活preBötC兴奋性神经元（定义为Vt 2和Sst神经元）和抑制性神经元（定义为Vgat神经元），并抑制和激活由转录因子Dbx 1定义的神经元，以了解preBötC和吞咽行为之间的协调。我们发现，刺激抑制性preBötC神经元并不能模拟吞咽水引起的吸气活动的过早关闭，这表明吞咽引起的吸气活动抑制并不直接由preBötC中的抑制性神经元介导。相比之下，刺激前BötC Dbx 1神经元延迟吞咽序列的喉关闭。Dbx 1神经元的抑制增加喉关闭持续时间和刺激Sst神经元的吞咽发生推到呼吸周期的后期，这表明来自preBötC的兴奋性神经元连接到喉运动神经元，并有助于吞咽的时间。有趣的是，延迟吞咽序列也是由慢性间歇性缺氧（CIH）引起的，CIH是一种睡眠呼吸暂停模型，1）已知会使吸气活动不稳定，2）与吞咽困难相关。当抑制Dbx 1神经元时，这种延迟不存在。我们认为稳定的preBötC对于正常吞咽模式的产生是必不可少的，并且中断可能导致阻塞性睡眠呼吸暂停中观察到的吞咽困难。
Swallowing is a vital behavior that must be coordinated with breathing. Both behaviors originate in the medulla, but the pathways responsible for their interactions have yet to be determined. It is hypothesized that inhibition from the medullary inspiratory driver, the pre–Bötzinger complex (preBötC), inhibits swallowing from occurring during times of inspiration. Using optogenetic stimulation of inhibitory and excitatory preBötC neurons, we provide evidence that the preBötC is involved in normal swallow production and coordination with breathing. We also suggest the preBötC is connected to the laryngeal motoneurons of the nucleus ambiguus (NA) and simulation of Dbx1 neurons delays laryngeal closure, disrupting the normal swallow sequence. This study explores neural pathways involved in swallowing–breathing coordination. The coordination of swallowing with breathing, in particular inspiration, is essential for homeostasis in most organisms. While much has been learned about the neuronal network critical for inspiration in mammals, the pre–Bötzinger complex (preBötC), little is known about how this network interacts with swallowing. Here we activate within the preBötC excitatory neurons (defined as Vglut2 and Sst neurons) and inhibitory neurons (defined as Vgat neurons) and inhibit and activate neurons defined by the transcription factor Dbx1 to gain an understanding of the coordination between the preBötC and swallow behavior. We found that stimulating inhibitory preBötC neurons did not mimic the premature shutdown of inspiratory activity caused by water swallows, suggesting that swallow-induced suppression of inspiratory activity is not directly mediated by the inhibitory neurons in the preBötC. By contrast, stimulation of preBötC Dbx1 neurons delayed laryngeal closure of the swallow sequence. Inhibition of Dbx1 neurons increased laryngeal closure duration and stimulation of Sst neurons pushed swallow occurrence to later in the respiratory cycle, suggesting that excitatory neurons from the preBötC connect to the laryngeal motoneurons and contribute to the timing of swallowing. Interestingly, the delayed swallow sequence was also caused by chronic intermittent hypoxia (CIH), a model for sleep apnea, which is 1) known to destabilize inspiratory activity and 2) associated with dysphagia. This delay was not present when inhibiting Dbx1 neurons. We propose that a stable preBötC is essential for normal swallow pattern generation and disruption may contribute to the dysphagia seen in obstructive sleep apnea.
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DOI：
10.1002/hed.21845
发表时间：
2011-10
影响因子：
2.9
作者：
Davenport, Paul W.;Bolser, Donald C.;Morris, Kendall F.
通讯作者：
Morris, Kendall F.
影响因子：
2.4
作者：
Rose KAR;Tickle PG;Elsey RM;Sellers WI;Crossley DA 2nd;Codd JR
通讯作者：
Codd JR
影响因子：
2.2
作者：
ATTENBURROW, DP;GOSS, VA
通讯作者：
GOSS, VA
影响因子：
5.5
作者：
DICK, TE;OKU, Y;CHERNIACK, NS
通讯作者：
CHERNIACK, NS
影响因子：
2.5
作者：
DOTY, RW;BOSMA, JF
通讯作者：
BOSMA, JF