Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre-Bötzinger complex: a computational modelling study.
Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre-Bötzinger complex: a computational modelling study.
复制标题
前 Bötzinger 复合体兴奋性神经网络节律爆发的钠和钙机制：一项计算模型研究。
DOI：
10.1111/ejn.12042
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Rybak,IlyaA
中科院分区：
文献类型：
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作者：
Jasinski,PatrickE;Molkov,YaroslavI;Shevtsova,NataliaA;Smith,JeffreyC;Rybak,IlyaA
在哺乳动物脑干中产生节律性爆发活动的神经机制，特别是在参与呼吸节律产生的前BötC复合体（pre-BötC）中，以及在突触抑制阻断后持续存在的脊髓（例如运动节律活动）中，仍然知之甚少。在含有前BötC的啮齿动物延髓切片中进行的实验研究确定了两种可能有助于产生节律性爆发的机制：一种基于持续性Na+电流（INaP），另一种涉及电压门控Ca 2+电流（伊卡）和Ca 2+激活的非特异性阳离子电流（ICAN），由细胞外和细胞内来源的细胞内Ca 2+积累激活。然而，这些机制在节律爆发中的参与和相对作用仍然存在争议。在这项理论/建模研究中，我们研究了单个细胞和突触互连兴奋性神经元的异质群体中产生的Na+依赖性和Ca 2+依赖性爆发，其中INaPandIC随机分布在群体中。我们分析了网络连接，离子型和代谢型突触机制，细胞内Ca 2+释放，和Na+/K+泵在不同条件下产生的节律性爆发的可能作用。我们发现，一个异质群体的兴奋性神经元可以在不同的振荡制度与爆发依赖于INaPand/orICAN，或独立于两者。我们表明，操作突发机制可能取决于神经元的兴奋，网络内的突触相互作用，和特定的离子电流的相对表达。在我们的模型中，多个振荡机制的存在及其状态依赖性可以解释在不同实验条件下在前BötC和其他脑干/脊髓回路中观察到的不同节律活动。
The neural mechanisms generating rhythmic bursting activity in the mammalian brainstem, particularly in the pre‐Bötzinger complex (pre‐BötC), which is involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor rhythmic activity) that persist after blockade of synaptic inhibition remain poorly understood. Experimental studies in rodent medullary slices containing the pre‐BötC identified two mechanisms that could potentially contribute to the generation of rhythmic bursting: one based on the persistent Na+current (INaP), and the other involving the voltage‐gated Ca2+current (ICa) and the Ca2+‐activated nonspecific cation current (ICAN), activated by intracellular Ca2+accumulated from extracellular and intracellular sources. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modelling study, we investigated Na+‐dependent and Ca2+‐dependent bursting generated in single cells and heterogeneous populations of synaptically interconnected excitatory neurons withINaPandICarandomly distributed within populations. We analysed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca2+release, and the Na+/K+pump in rhythmic bursting generated under different conditions. We show that a heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent onINaPand/orICAN, or independent of both. We demonstrate that the operating bursting mechanism may depend on neuronal excitation, synaptic interactions within the network, and the relative expression of particular ionic currents. The existence of multiple oscillatory regimes and their state dependence demonstrated in our models may explain different rhythmic activities observed in the pre‐BötC and other brainstem/spinal cord circuits under different experimental conditions.