Department of Biology, Washington and Lee University, Lexington, VA, USA.
Respir Physiol Neurobiol. 2013 Feb 1;185(3):582-92. doi: 10.1016/j.resp.2012.11.013. Epub 2012 Nov 30.
Neuromodulators, such as amines and neuropeptides, alter the activity of neurons and neuronal networks. In this work, we investigate how neuromodulators, which activate G(q)-protein second messenger systems, can modulate the bursting frequency of neurons in a critical portion of the respiratory neural network, the pre-Bötzinger complex (preBötC). These neurons are a vital part of the ponto-medullary neuronal network, which generates a stable respiratory rhythm whose frequency is regulated by neuromodulator release from the nearby Raphe nucleus. Using a simulated 50-cell network of excitatory preBötC neurons with a heterogeneous distribution of persistent sodium conductance and Ca(2+), we determined conditions for frequency modulation in such a network by simulating interaction between Raphe and preBötC nuclei. We found that the positive feedback between the Raphe excitability and preBötC activity induces frequency modulation in the preBötC neurons. In addition, the frequency of the respiratory rhythm can be regulated via phasic release of excitatory neuromodulators from the Raphe nucleus. We predict that the application of a G(q) antagonist will eliminate this frequency modulation by the Raphe and keep the network frequency constant and low. In contrast, application of a G(q) agonist will result in a high frequency for all levels of Raphe stimulation. Our modeling results also suggest that high [K(+)] requirement in respiratory brain slice experiments may serve as a compensatory mechanism for low neuromodulatory tone.
神经调质，如胺类和神经肽，可改变神经元和神经网络的活动。在这项工作中，我们研究了激活 G(q)-蛋白第二信使系统的神经调质如何调节呼吸神经网络关键部分（前脑桥复合核（preBötC））中神经元的爆发频率。这些神经元是延髓网络的重要组成部分，延髓网络产生稳定的呼吸节律，其频率受来自附近中缝核的神经调质释放的调节。使用具有持久性钠电导和 Ca(2+) 异质性分布的模拟 50 个兴奋性 preBötC 神经元的网络，我们通过模拟 Raphe 和 preBötC 核之间的相互作用，确定了这种网络中频率调制的条件。我们发现，Raphe 兴奋性和 preBötC 活性之间的正反馈诱导 preBötC 神经元中的频率调制。此外，呼吸节律的频率可以通过 Raphe 核中兴奋性神经调质的相发性释放来调节。我们预测，应用 G(q) 拮抗剂将消除 Raphe 的这种频率调制，并使网络频率保持恒定和低。相比之下，应用 G(q) 激动剂将导致 Raphe 刺激的所有水平的高频。我们的建模结果还表明，呼吸脑片实验中高 [K(+)] 需求可能是低神经调质张力的补偿机制。
