Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus
Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus
复制标题
DOI：
10.1113/jphysiol.2008.155861
复制
发表时间：
2008-12-01
影响因子：
5.5
通讯作者：
Bevan, Mark D.
中科院分区：
文献类型：
--
作者：
Atherton, Jeremy F.;Wokosin, David L.;Bevan, Mark D.
丘脑底核 (STN) 的活动与运动密切相关，部分是由驱动自主放电的电压依赖性 Na(+) (Na(v)) 通道产生的。为了确定 STN 神经元动作电位启动和传播的原理，使用 2 光子激光扫描显微镜来指导大鼠脑切片中紧密密封的全细胞体细胞和松散密封的细胞附着的轴突/树突膜片钳记录和隔室选择性离子通道操作。首先在与无髓鞘轴突起始段最接近的区域（由高尔基体和锚蛋白 G 标记定义）中检测到动作电位。启动后，动作电位可靠地传播到轴突和体树突区，传导速度分别类似于 5 m s(-1) 和类似于 0.7 m s(-1)。轴突在轴突起始段以内或之外被截断的神经元产生的动作电位没有显着差异。然而，使用低[Na(+)] ACSF 或选择性Na(v) 通道阻滞剂河豚毒素，轴突起始段和体细胞而非树突或更远端轴突应用始终使动作电位阈值去极化。最后，GABA 的体细胞树突而非轴突应用引起了大而快速的抑制电流，这与电子显微镜分析一致，这表明体细胞树突区室是假定的抑制输入的主要目标。这些数据与以下结论一致：在 STN 神经元中，轴突初始段和体细胞表达过量的 Na(v) 通道以产生自主活动，而体细胞树突 GABA(A) 受体的突触激活调节动作电位的轴突启动。
The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of similar to 5 m s(-1) and similar to 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.