The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurosci. 2012 May 16;32(20):6859-68. doi: 10.1523/JNEUROSCI.0267-12.2012.
In the vertebrate retina, neuronal circuitry required for visual perception is organized within specific laminae. Photoreceptors convey external visual information to bipolar and horizontal cells at triad ribbon synapses established within the outer plexiform layer (OPL), initiating retinal visual processing. However, the molecular mechanisms that organize these three classes of neuronal processes within the OPL, thereby ensuring appropriate ribbon synapse formation, remain largely unknown. Here we show that mice with null mutations in Sema6A or PlexinA4 (PlexA4) exhibit a pronounced defect in OPL stratification of horizontal cell axons without any apparent deficits in bipolar cell dendrite or photoreceptor axon targeting. Furthermore, these mutant horizontal cells exhibit aberrant dendritic arborization and reduced dendritic self-avoidance within the OPL. Ultrastructural analysis shows that the horizontal cell contribution to rod ribbon synapse formation in PlexA4⁻/⁻ retinas is disrupted. These findings define molecular components required for outer retina lamination and ribbon synapse formation.
在脊椎动物的视网膜中，用于视觉感知的神经元回路组织在特定的层内。光感受器通过在外丛状层（OPL）中建立的三联体带状突触将外部视觉信息传递给双极细胞和水平细胞，从而启动视网膜视觉处理。然而，将这三类神经元过程组织在 OPL 中以确保适当的带状突触形成的分子机制在很大程度上仍然未知。在这里，我们展示了 Sema6A 或 PlexinA4（PlexA4）缺失突变的小鼠在 OPL 中水平细胞轴突的分层有明显缺陷，而双极细胞树突或光感受器轴突靶向没有任何明显缺陷。此外，这些突变的水平细胞在 OPL 内表现出异常的树突分支和减少的树突自回避。超微结构分析表明，PlexA4⁻/⁻ 视网膜中杆状带突触形成的水平细胞贡献被破坏。这些发现定义了形成外视网膜分层和带状突触形成所必需的分子成分。
