Analysis and modeling of ensemble recordings from respiratory pre-motor neurons indicate changes in functional network architecture after acute hypoxia

Analysis and modeling of ensemble recordings from respiratory pre-motor neurons indicate changes in functional network architecture after acute hypoxia
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DOI:
10.3389/fncom.2010.00131
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发表时间:
2010-09-01
影响因子:
3.2
通讯作者:
Baekey, David M.
Baekey, David M.
中科院分区:
医学4区
文献类型:
--
作者:
Galan, Roberto Fernandez;Dick, Thomas E.;Baekey, David M.

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我们结合神经生理学记录、统计分析和计算模型来研究脑干中呼吸网络的动力学。使用多电极阵列,我们在灌流的原位大鼠准备中记录了呼吸神经元的集合,这些准备产生了自发的呼吸模式,重点是吸气前运动神经元。我们比较了短暂低氧刺激前后这些神经元的放电率和神经元同步性。我们观察到刺激后的棘波数量显著减少,部分原因是呼吸模式的一过性减慢。然而,中位数的棘波间期没有改变,这表明神经元的放电阈值没有受到影响,但突触输入受到了影响。对棘波序列之间同步性的Bootstrap分析表明,在短暂缺氧之前和之后,神经元对之间高达45%(但通常不到5%)的一致棘波不是偶然的。最有可能的是,这种同步是由运动前群体的共同突触输入造成的,这是随机同步的一个例子。在短暂的低氧后,大多数配对的同步性较差,尽管有些配对的同步性更强,这表明刺激后呼吸网络短暂地重新连接。为了研究这一假设,我们创建了一个简单的计算模型,沿着吸气路径具有前馈发散连接。假设(1)所有突触前细胞的发散投射数量并不相同,而是跨越了很大的范围;(2)刺激增加了网络顶端的抑制;这个模型再现了在我们的实验数据中观察到的低氧刺激后放电频率的降低和引导校正的同步性。
We have combined neurophysiologic recording, statistical analysis, and computational modeling to investigate the dynamics of the respiratory network in the brainstem. Using a multielectrode array, we recorded ensembles of respiratory neurons in perfused in situ rat preparations that produce spontaneous breathing patterns, focusing on inspiratory pre-motor neurons. We compared firing rates and neuronal synchronization among these neurons before and after a brief hypoxic stimulus. We observed a significant decrease in the number of spikes after stimulation, in part due to a transient slowing of the respiratory pattern. However, the median interspike interval did not change, suggesting that the firing threshold of the neurons was not affected but rather the synaptic input was. A bootstrap analysis of synchrony between spike trains revealed that both before and after brief hypoxia, up to 45% (but typically less than 5%) of coincident spikes across neuronal pairs was not explained by chance. Most likely, this synchrony resulted from common synaptic input to the pre-motor population, an example of stochastic synchronization. After brief hypoxia most pairs were less synchronized, although some were more, suggesting that the respiratory network was transiently "rewired" after the stimulus. To investigate this hypothesis, we created a simple computational model with feed-forward divergent connections along the inspiratory pathway. Assuming that (1) the number of divergent projections was not the same for all presynaptic cells, but rather spanned a wide range and (2) that the stimulus increased inhibition at the top of the network; this model reproduced the reduction in firing rate and bootstrap-corrected synchrony subsequent to hypoxic stimulation observed in our experimental data.