Godinho Leanne, Mumm Jeff S, Williams Philip R, Schroeter Eric H, Koerber Amy, Park Seung W, Leach Steven D, Wong Rachel O L
Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8108, St Louis, MO 63110, USA.
Development. 2005 Nov;132(22):5069-79. doi: 10.1242/dev.02075.
Cellular mechanisms underlying the precision by which neurons target their synaptic partners have largely been determined based on the study of projection neurons. By contrast, little is known about how interneurons establish their local connections in vivo. Here, we investigated how developing amacrine interneurons selectively innervate the appropriate region of the synaptic neuropil in the inner retina, the inner plexiform layer (IPL). Increases (ON) and decreases (OFF) in light intensity are processed by circuits that are structurally confined to separate ON and OFF synaptic sublaminae within the IPL. Using transgenic zebrafish in which the majority of amacrine cells express fluorescent protein, we determined that the earliest amacrine-derived neuritic plexus formed between two cell populations whose somata, at maturity, resided on opposite sides of this plexus. When we followed the behavior of individual amacrine cells over time, we discovered that they exhibited distinct patterns of structural dynamics at different stages of development. During cellular migration, amacrine cells exhibited an exuberant outgrowth of neurites that was undirected. Upon reaching the forming IPL, neurites extending towards the ganglion cell layer were relatively more stable. Importantly, when an arbor first formed, it preferentially ramified in either the inner or outer IPL corresponding to the future ON and OFF sublaminae, and maintained this stratification pattern. The specificity by which ON and OFF amacrine interneurons innervate their respective sublaminae in the IPL contrasts with that observed for projection neurons in the retina and elsewhere in the central nervous system.
神经元精准靶向其突触伙伴的细胞机制，很大程度上是基于对投射神经元的研究而确定的。相比之下，对于中间神经元如何在体内建立其局部连接却知之甚少。在这里，我们研究了发育中的无长突中间神经元如何选择性地支配视网膜内层、内网状层（IPL）中突触神经毡的适当区域。光强度的增加（开）和减少（关）由结构上局限于IPL内单独的开和关突触亚层的回路处理。利用大多数无长突细胞表达荧光蛋白的转基因斑马鱼，我们确定最早的无长突衍生神经丛形成于两个细胞群体之间，这两个群体成熟时的胞体位于该神经丛的两侧。当我们追踪单个无长突细胞随时间的行为时，我们发现它们在发育的不同阶段表现出不同的结构动力学模式。在细胞迁移过程中，无长突细胞表现出无定向的旺盛神经突生长。到达正在形成的IPL时，向神经节细胞层延伸的神经突相对更稳定。重要的是，当一个树突首次形成时，它优先在对应于未来开和关亚层的IPL内层或外层分支，并维持这种分层模式。开和关无长突中间神经元在IPL中支配其各自亚层的特异性，与在视网膜和中枢神经系统其他部位观察到的投射神经元的特异性形成对比。
