Burst discharge in primary sensory neurons: Triggered by subthreshold oscillations, maintained by depolarizing afterpotentials
Burst discharge in primary sensory neurons: Triggered by subthreshold oscillations, maintained by depolarizing afterpotentials
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DOI：
10.1523/jneurosci.22-03-01187.2002
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发表时间：
2002-02-01
影响因子：
5.3
通讯作者：
Devor, M
中科院分区：
文献类型：
--
作者：
Amir, R;Michaelis, M;Devor, M
背根神经节（DRG）神经元胞体索马内异位产生的传入放电可能在正常感觉中发挥作用，并与神经损伤后的感觉异常和疼痛有关。这种活动是严重依赖于阈下膜电位振荡;振荡正弦波，达到阈值触发低频列车的间歇性尖峰。然而，异位放电也可能进入高频爆发模式，特别是在神经病变的情况下。爆发极大地放大了整体的异位弹幕。在本报告中，我们表明，阈下振荡和爆发放电发生在体内，因为它们在体外。然后，我们表明，虽然在每个突发的第一个尖峰是由一个振荡的正弦波触发，在突发内发射维持简短的再生后尖峰去极化后电位（DAP）。使用数值模拟来识别反弹DAP背后的细胞过程，从而识别尖峰爆发的机制。最后，我们表明，缓慢的斜坡和保持（紧张）去极化的排序，发生在DRG神经元在生理相关的事件能够触发持续的异位爆裂，但只有在细胞的阈下振荡行为。振荡和DAP是异位爆发放电的基本基质。因此，任何对离子通道合成和运输的细胞调节实现正常感觉的方式的考虑，以及当被破坏时引起神经性疼痛的方式，都必须考虑这种调节对振荡和爆发的影响。
Afferent discharge generated ectopically in the cell soma of dorsal root ganglion (DRG) neurons may play a role in normal sensation, and it contributes to paraesthesias and pain after nerve trauma. This activity is critically dependent on subthreshold membrane potential oscillations; oscillatory sinusoids that reach threshold trigger low-frequency trains of intermittent spikes. Ectopic firing may also enter a high-frequency bursting mode, however, particularly in the event of neuropathy. Bursting greatly amplifies the overall ectopic barrage. In the present report we show that subthreshold oscillations and burst discharge occur in vivo, as they do in vitro. We then show that although the first spike in each burst is triggered by an oscillatory sinusoid, firing within bursts is maintained by brief regenerative post-spike depolarizing afterpotentials (DAPs). Numerical simulations were used to identify the cellular process underlying rebound DAPs, and hence the mechanism of the spike bursts. Finally, we show that slow ramp and hold (tonic) depolarizations of the sort that occur in DRG neurons during physiologically relevant events are capable of triggering sustained ectopic bursting, but only in cells with subthreshold oscillatory behavior. Oscillations and DAPs are an essential substrate of ectopic burst discharge. Therefore, any consideration of the ways in which cellular regulation of ion channel synthesis and trafficking implement normal sensation and, when disrupted, bring about neuropathic pain must take into account the effects of this regulation on oscillations and bursting.