Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan 112.
J Comp Neurol. 2012 Nov 1;520(16):3650-72. doi: 10.1002/cne.23119.
Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K⁺ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²⁺ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²⁺ -dependent electrical activity of pioneer axons and play important roles during axon pathfinding.
精确的轴突寻路对于发育过程中初始神经元网络的建立至关重要。先驱轴突在没有预先存在的轴突帮助的情况下进行导航，并为随后的轴突投射铺平道路。电压门控离子通道构成先驱轴突的固有电活动，并调节轴突寻路。为了阐明先驱轴突中存在哪些通道分子，进行了免疫组织化学分析，以检查 9 个大鼠前脑发育中的轴突束中的 14 种电压门控离子通道（Kv1.1-Kv1.3、Kv3.1-Kv3.4、Kv4.3、Cav1.2、Cav1.3、Cav2.2、Nav1.2、Nav1.6 和 Nav1.9），包括视神经、胼胝体、皮质传出纤维、丘脑皮质轴突、外侧嗅束、海马隔投射、前连合、海马连合和内侧纵束。我们发现 A 型 K⁺通道 Kv3.4 存在于先驱轴突和早期跟随轴突中，L 型 Ca²⁺通道 Cav1.2 存在于先驱轴突和早期和晚期跟随轴突中。在空间上，Kv3.4 和 Cav1.2 与先驱神经元和先驱轴突的标志物（如结直肠癌缺失基因（DCC））在大多数检查的纤维束中存在共定位。在时间上，Kv3.4 和 Cav1.2 在大多数纤维束中在轴突寻路过程中表达丰富，但在突触发生开始时下调。相比之下，延迟整流钾通道（例如 Kv1.1）和 Nav 通道（例如 Nav1.2）在先驱轴突的寻路过程中不存在于这些纤维束（胼胝体除外）。这些数据表明，两种高电压激活的离子通道 Kv3.4 和 Cav1.2 可能共同作用，控制先驱轴突的 Ca²⁺依赖性电活动，并在轴突寻路过程中发挥重要作用。
