Department of Neurobiology, University of California, Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA.
Department of Neurobiology, University of California, Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA.
Neuron. 2020 May 6;106(3):482-497.e4. doi: 10.1016/j.neuron.2020.02.005. Epub 2020 Mar 3.
We assessed the mechanism of mammalian breathing rhythmogenesis in the preBötzinger complex (preBötC) in vitro, where experimental tests remain inconsistent with hypotheses of canonical rhythmogenic cellular or synaptic mechanisms, i.e., pacemaker neurons or inhibition. Under rhythmic conditions, in each cycle, an inspiratory burst emerges as (presumptive) preBötC rhythmogenic neurons transition from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration (for ∼50-500 ms), which can trigger inspiratory bursts that propagate to motoneurons. In nonrhythmic conditions, antagonizing GABA receptors can initiate this synchronization while inducing a higher conductance state in nonrhythmogenic preBötC output neurons. Our analyses uncover salient features of preBötC network dynamics where inspiratory bursts arise when and only when the preBötC rhythmogenic subpopulation strongly synchronizes to drive output neurons. Furthermore, downstream propagation of preBötC network activity, ultimately to motoneurons, is dependent on the strength of input synchrony onto preBötC output neurons exemplifying synchronous propagation of network activity.
我们评估了哺乳动物呼吸节律发生在 PreBötzinger 复合体（preBötC）中的机制，在体外，实验测试与经典节律发生细胞或突触机制的假设不一致，即起搏神经元或抑制。在有节奏的条件下，在每个周期中，吸气爆发出现，因为（假定的）preBötC 节律发生神经元从无关联的群体峰电位活动过渡到在预吸气期间变得越来越同步（约 50-500ms），这可以触发传播到运动神经元的吸气爆发。在非节律条件下，拮抗 GABA 受体可以引发这种同步，同时诱导非节律发生的 preBötC 输出神经元中的更高电导状态。我们的分析揭示了 preBötC 网络动力学的显著特征，即当 preBötC 节律发生亚群强烈同步以驱动输出神经元时，吸气爆发才会出现。此外，preBötC 网络活动的下游传播，最终到运动神经元，取决于输入到 preBötC 输出神经元的同步强度，这体现了网络活动的同步传播。
