Interactions of persistent sodium and calcium-activated nonspecific cationic currents yield dynamically distinct bursting regimes in a model of respiratory neurons.
Interactions of persistent sodium and calcium-activated nonspecific cationic currents yield dynamically distinct bursting regimes in a model of respiratory neurons.
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DOI：
10.1007/s10827-010-0311-y
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发表时间：
2011-10
影响因子：
1.2
通讯作者：
Rubin, Jonathan E.
中科院分区：
文献类型：
--
作者：
Dunmyre, Justin R.;Del Negro, Christopher A.;Rubin, Jonathan E.
关键词：
前BötC复合体（preBötC）是哺乳动物脑干内的一种异质神经元网络，实验发现它能产生强大的同步爆发，驱动呼吸节律的吸气相。在每个前BötC神经元中都观察到持续性钠（NaP）电流，并且重要的建模工作已经表征了其对前BötC中方波爆发的贡献。最近的实验工作表明，前BötC内的神经元被赋予钙激活的非特异性阳离子（CAN）电流，该电流由谷氨酸启动的信号级联激活。在preBötC模型中，CAN电流被证明可以促进经历去极化阻滞（DB突发）的鲁棒突发。我们考虑一个自耦合模型神经元，我们表示为一个单一的隔间根据我们的实验发现的电紧张性的紧凑性，根据变化的gNaP，NaP电流的电导，和gCAN，CAN电流的电导。改变这两个电导产生一系列的活动模式，包括静止，紧张活动，方波爆发，DB爆发，以及一种新的混合方波和DB爆发，这与我们在实验准备中观察到的活动相匹配。我们阐明这些动态的机制，以及这些制度之间的过渡和双稳态的发生，通过应用分岔分析和慢-快分解的数学工具。基于NaP和CAN电流的普遍性，我们预计，我们提出的用于建模它们之间相互作用的可推广框架可能与preBötC之外的其他脑区的节律性也相关。
The preBötzinger complex (preBötC) is a heterogeneous neuronal network within the mammalian brainstem that has been experimentally found to generate robust, synchronous bursts that drive the inspiratory phase of the respiratory rhythm. The persistent sodium (NaP) current is observed in every preBötC neuron, and significant modeling effort has characterized its contribution to square-wave bursting in the preBötC. Recent experimental work demonstrated that neurons within the preBötC are endowed with a calcium-activated nonspecific cationic (CAN) current that is activated by a signaling cascade initiated by glutamate. In a preBötC model, the CAN current was shown to promote robust bursts that experience depolarization block (DB bursts). We consider a self-coupled model neuron, which we represent as a single compartment based on our experimental finding of electrotonic compactness, under variation of gNaP, the conductance of the NaP current, and gCAN, the conductance of the CAN current. Varying these two conductances yields a spectrum of activity patterns, including quiescence, tonic activity, square-wave bursting, DB bursting, and a novel mixture of square-wave and DB bursts, which match well with activity that we observe in experimental preparations. We elucidate the mechanisms underlying these dynamics, as well as the transitions between these regimes and the occurrence of bistability, by applying the mathematical tools of bifurcation analysis and slow-fast decomposition. Based on the prevalence of NaP and CAN currents, we expect that the generalizable framework for modeling their interactions that we present may be relevant to the rhythmicity of other brain areas beyond the preBötC as well.
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