Neocortical Chandelier Cells Developmentally Shape Axonal Arbors through Reorganization but Establish Subcellular Synapse Specificity without Refinement
Neocortical Chandelier Cells Developmentally Shape Axonal Arbors through Reorganization but Establish Subcellular Synapse Specificity without Refinement
复制标题
DOI：
10.1523/eneuro.0057-17.2017
复制
发表时间：
2017-05-01
期刊：
影响因子：
3.4
通讯作者：
Taniguchi, Hiroki
中科院分区：
文献类型：
--
作者：
Steinecke, Andre;Hozhabri, Ellie;Taniguchi, Hiroki
不同类型的皮层中间神经元（INs）介导各种抑制性控制机制来平衡和塑造网络活动。不同的IN亚型发展独特的组织轴突乔木，支配兴奋性主神经元（PN）的不同亚细胞区室，这对确定其输出特性至关重要。然而，它仍然知之甚少，他们如何建立这种特殊的轴突组织和突触连接在发展过程中。在这里，利用遗传标记的IN祖细胞，我们研究了轴突的乔木和突触连接形成的小鼠枝形细胞（ChCs），神经支配轴突起始段（AIS）的PN，从而有力地调节他们的穗产生的发育过程。我们通过光学显微镜的定量分析表明，ChCs过度生长，随后细化轴突分支以及静脉曲张。有趣的是，我们发现，尽管除了AIS上的轴突静脉曲张外，还有大量的轴突静脉曲张在AIS上形成，但在整个发育过程中，突触前标记物主要与AIS上的标记物科洛共定位。免疫电镜（IEM）分析也表明，只有与AIS并列的静脉曲张才含有突触前结构。这些结果表明，ChCs的亚细胞突触特异性是遗传预定的，而轴突的几何形状通过重塑。定位于AIS的分子线索可能调节ChCs的靶点识别和突触形成。
Diverse types of cortical interneurons (INs) mediate various kinds of inhibitory control mechanisms to balance and shape network activity. Distinct IN subtypes develop uniquely organized axonal arbors that innervate different subcellular compartments of excitatory principal neurons (PNs), which critically contribute to determining their output properties. However, it remains poorly understood how they establish this peculiar axonal organization and synaptic connectivity during development. Here, taking advantage of genetic labeling of IN progenitors, we examined developmental processes of axonal arbors and synaptic connections formed by murine chandelier cells (ChCs), which innervate axon initial segments (AISs) of PNs and thus powerfully regulate their spike generation. Our quantitative analysis by light microscopy revealed that ChCs overgrow and subsequently refine axonal branches as well as varicosities. Interestingly, we found that although a significant number of axonal varicosities are formed off AISs in addition to on AISs, presynaptic markers are predominantly colo calized with those on AISs throughout development. Immunoelectron microscopic (IEM) analysis also demonstratedthat only varicosities apposed to AISs contain presynaptic profiles. These results suggest that subcellular synapse specificity of ChCs is genetically predetermined while axonal geometry is shaped through remodeling. Molecular cueslocalized at AISs may regulate target recognition and synapse formation by ChCs.