Phasic inhibition as a mechanism for generation of rapid respiratory rhythms
Phasic inhibition as a mechanism for generation of rapid respiratory rhythms
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DOI：
10.1073/pnas.1711536114
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发表时间：
2017-11-28
影响因子：
11.1
通讯作者：
Silver, Jerry
中科院分区：
文献类型：
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作者：
Cregg, Jared M.;Chu, Kevin A.;Silver, Jerry
中枢神经网络在整个生命过程中持续运作以控制呼吸，但对调节呼吸频率的机制知之甚少。吸气是由延髓腹外侧的前Botzinger复合体产生的，在那里，人们认为兴奋会增加吸气频率，抑制会导致呼吸暂停。为了测试该模型，我们使用体外光遗传学方法来刺激选择的后脑神经元群体并表征它们如何调节频率。出乎意料的是，我们发现，抑制所需的刺激Phox2b谱系，推定的CO2化学敏感神经元引起的频率增加。作为一个机制的解释抑制依赖性增加频率，我们发现，相位刺激抑制神经元可以增加吸气频率通过抑制后反弹。我们目前的证据表明，Phox2b介导的频率增加是由反弹兴奋后，抑制性突触凌空中继呼气。因此，虽然人们普遍认为，吸气和呼气之间的抑制只是防止在拮抗阶段的活动，我们反而提出了一个模型，通过抑制后反弹兴奋抑制耦合实际上产生快速模式的吸气。
Central neural networks operate continuously throughout life to control respiration, yet mechanisms regulating ventilatory frequency are poorly understood. Inspiration is generated by the pre-Botzinger complex of the ventrolateral medulla, where it is thought that excitation increases inspiratory frequency and inhibition causes apnea. To test this model, we used an in vitro optogenetic approach to stimulate select populations of hindbrain neurons and characterize how they modulate frequency. Unexpectedly, we found that inhibition was required for increases in frequency caused by stimulation of Phox2b-lineage, putative CO2-chemosensitive neurons. As a mechanistic explanation for inhibition-dependent increases in frequency, we found that phasic stimulation of inhibitory neurons can increase inspiratory frequency via postinhibitory rebound. We present evidence that Phox2b-mediated increases in frequency are caused by rebound excitation following an inhibitory synaptic volley relayed by expiration. Thus, although it is widely thought that inhibition between inspiration and expiration simply prevents activity in the antagonistic phase, we instead propose a model whereby inhibitory coupling via postinhibitory rebound excitation actually generates fast modes of inspiration.