Feedforward inhibition contributes to the control of epileptiform propagation speed
Feedforward inhibition contributes to the control of epileptiform propagation speed
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DOI：
10.1523/jneurosci.0145-07.2007
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发表时间：
2007-03-28
影响因子：
5.3
通讯作者：
Yuste, Rafael
中科院分区：
文献类型：
--
作者：
Trevelyan, Andrew J.;Sussillo, David;Yuste, Rafael
对于癫痫样事件是如何激活皮层回路的，我们仍然知之甚少。此外，癫痫样放电在体内和体外的传播速度可以在几个数量级（0.1-100 mm/s）上变化，这是一个难以用单一机制解释的范围。我们以前表明，癫痫样传播的新皮层切片是反对一个强大的前馈抑制提前发作波。当这种前馈抑制是完整的，癫痫样传播非常缓慢（类似于100 μ m/s）。我们现在调查是否在这种抑制约束的变化也可以解释更快的传播速度。我们利用了一个非常典型的模式，在零镁（0 Mg 2+）癫痫模型的发作活动的演变。随着每个连续的发作事件，发作前抑制性弹幕的数量下降，并与这种变化平行，传播速度增加。在1000倍速度范围内，两种测量值之间存在高度显著的相关性（p < 0.001），表明前馈抑制是癫痫样传播速度的主要决定因素。我们建议，传播的速度是由招聘步骤的程度，这反过来又是如何成功的前馈抑制约束包含兴奋性驱动。因此，一个单一的机制可以解释在体外和体内观察到的癫痫样事件的传播速度范围很广。
It is still poorly understood how epileptiform events can recruit cortical circuits. Moreover, the speed of propagation of epileptiform discharges in vivo and in vitro can vary over several orders of magnitude (0.1-100 mm/s), a range difficult to explain by a single mechanism. We previously showed how epileptiform spread in neocortical slices is opposed by a powerful feedforward inhibition ahead of the ictal wave. When this feedforward inhibition is intact, epileptiform spreads very slowly (similar to 100 mu m/s). We now investigate whether changes in this inhibitory restraint can also explain much faster propagation velocities. We made use of a very characteristic pattern of evolution of ictal activity in the zero magnesium (0 Mg2+) model of epilepsy. With each successive ictal event, the number of preictal inhibitory barrages dropped, and in parallel with this change, the propagation velocity increased. There was a highly significant correlation (p < 0.001) between the two measures over a 1000-fold range of velocities, indicating that feedforward inhibition was the prime determinant of the speed of epileptiform propagation. We propose that the speed of propagation is set by the extent of the recruitment steps, which in turn is set by how successfully the feedforward inhibitory restraint contains the excitatory drive. Thus, a single mechanism could account for the wide range of propagation velocities of epileptiform events observed in vitro and in vivo.