Models of respiratory rhythm generation in the pre-Botzinger complex. II. Populations of coupled pacemaker neurons
Models of respiratory rhythm generation in the pre-Botzinger complex. II. Populations of coupled pacemaker neurons
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DOI：
10.1152/jn.1999.82.1.398
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发表时间：
1999-07-01
影响因子：
2.5
通讯作者：
Smith, JC
中科院分区：
文献类型：
--
作者：
Butera, RJ;Rinzel, J;Smith, JC
我们已经提出了模型的离子基础振荡爆发呼吸起搏器神经元在前波青格复合体。在本文中，我们研究了这些模型神经元在兴奋性氨基酸介导的突触耦合和收敛性突触输入控制下的频率控制和同步。对相同细胞对的模拟结果表明，增强的张力刺激增加了同步爆发的频率，而增强的神经元间兴奋耦合强度则降低了同步爆发的频率。对50-500个异质爆发神经元的模拟显示了与体外实验相似的耦合效应：耦合增加了平均爆发持续时间，降低了平均爆发频率。爆发同步发生在很宽的固有频率范围内（0.1-1 Hz），甚至在只有10%的细胞本质上爆发的人群中。弱耦合、极端参数非均匀性和低水平的去极化输入可能导致种群的非同步，并产生准周期态。稀疏耦合的引入并不影响突发同步，尽管它确实使突发间隔在周期之间更加不规则。在种群水平上，参数异质性和兴奋性耦合协同作用增加了动态输入范围：与单个模型细胞相比，鲁棒同步爆破在更大的参数空间范围内持续存在（就平均去极化输入而言）。这种扩展的动态范围为rhp爆发细胞群体表明，细胞异质性是功能上有利的。我们的模型系统解释了在新生大鼠体外脑干切片的前波青格复合体中发现的吸气(I)爆裂细胞的固有频率和尖峰模式的范围。群体中神经元的尖峰发生时间存在时间分散，预测这是由于神经元内在特性的异质性，神经元在群体爆发之前（前I）、之后（后I）或之后（前I）开始尖峰。对该模型的一些预测提出了实验检验。
We have proposed models for the ionic basis of oscillatory bursting of respiratory pacemaker neurons in the pre-Botzinger complex. In this paper, we investigate the frequency control and synchronization of these model neurons when coupled by excitatory amino-acid-mediated synapses and controlled by convergent synaptic inputs modeled as tonic excitation. Simulations of pairs of identical cells reveal that increasing tonic excitation increases the frequency of synchronous bursting while increasing thp strength of excitatory coupling between the neurons decreases the frequency of synchronous bursting Low levels of coupling extend the range of values of tonic excitation where synchronous bursting is found. Simulations of a heterogeneous population of 50-500 bursting neurons reveal coupling effects similar tn those found experimentally in vitro: coupling increases the mean burst duration and decreases the mean burst frequency. Burst synchronization occurred over a wide range of intrinsic frequencies (0.1-1 Hz) and even in populations where as few as 10% of the cells were intrinsically bursting. Weak coupling, extreme parameter heterogeneity, and low levels of depolarizing input could contribute to the desynchronization of the population and give rise to quasiperiodic states. The introduction of sparse coupling did not affect the burst synchrony, although it did make the interburst intervals more irregular from cycle to cycle. At a population level, both parameter heterogeneity, and excitatory coupling synergistically combine to increase the dynamic input range: robust synchronous bursting persisted across a much greater range of parameter space (in terms of mean depolarizing input) than that of a single model cell. This extended dynamic range for rhp bursting cell population indicates that cellular heterogeneity is functionally advantageous. Our modeled system accounts for the range of intrinsic frequencies and spiking patterns of inspiratory (I) bursting cells found in the pre-Botzinger complex in neonatal rat brain stem slices in vitro. There is a temporal dispersion in the spiking onset times of neurons in the population, predicted to be due to heterogeneity in intrinsic neuronal properties, with neurons starting to spike before (pre-I), with (I), or after (late-I) the onset of the population burst. Experimental tests for a number of the model's predictions are proposed.