哺乳动物呼吸与吞咽中枢模式发生器之间突触相互作用的建模

文献信息

中文摘要

背景： 呼吸和吞咽是紧密耦合的运动行为，其执行依赖于两个脑干中枢模式发生器（R-CPG、Sw-CPG）的协调活动。我们提出了一个机制性神经网络模型来捕捉这种协调。方法：该模型通过逐步扩展R-CPG和Sw-CPG模块的突触连接构建，每个模块由神经元群体节点组成，其动力学包含放电率适应。两个CPG的节律发生核心均实现为独立运作的半中心振荡器。结果：与伴随的离体灌注脑干制备实验记录一致，对喉上神经（SLN）的模拟10秒感觉驱动可靠地引发虚构的序列性吞咽爆发，并伴有声门闭合和吸气活动抑制。短SLN刺激（100毫秒）产生孤立的单次吞咽，并重置呼吸振荡器的相位。模型动力学的相空间分析为这种SLN诱发的呼吸相位重置提供了额外见解。与先前实验观察一致，模拟的脑桥抑制重现了呼吸暂停，并在序列性吞咽期间消除了吞咽相关的声门闭合。对特定网络通路中突触权重的系统扰动识别出脆弱连接，其减弱可重现临床相关的呼吸-吞咽障碍，包括误吸。结论：该模型由此产生机制性预测，可能为以呼吸-吞咽协调受损为特征的疾病的治疗干预设计提供信息。

英文摘要

Breathing and swallowing are tightly coupled motor behaviors whose execution depends on the coordinated activity of two brainstem central pattern generators (R-CPG, Sw-CPG). We present a mechanistic neural network model that captures this coordination. The model was built by incrementally expanding the synaptic connectivity of R-CPG and Sw-CPG modules, each composed of neuronal population nodes whose dynamics incorporate firing rate adaptation. The rhythmogenic cores of both CPGs are implemented as half-center oscillators operating independently. In agreement with accompanying experimental recordings from an in situ perfused brainstem preparation, a simulated 10 s sensory drive to the superior laryngeal nerve (SLN) reliably elicits fictive sequential swallowing bursts accompanied by glottal closure and suppression of inspiratory activity. Short SLN stimuli (100 ms) produce isolated single swallows that reset the phase of the respiratory oscillator. Phase space analysis of the model dynamics offers additional insight into this SLN-evoked respiratory phase resetting. Consistent with prior experimental observations, simulated pontine inhibition reproduces apneusis and abolish swallowing-related glottal closure during sequential swallowing. Systematic perturbation of synaptic weights across specific network pathways identifies vulnerable connections whose weakening recapitulates clinically relevant breathing-swallowing disorders, including aspiration. The model thereby generates mechanistic predictions that may inform the design of therapeutic interventions for conditions characterized by impaired breathing-swallowing coordination.