Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Division of Molecular and Developmental Biology, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Nat Commun. 2016 Sep 2;7:12650. doi: 10.1038/ncomms12650.
Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process.
谷氨酸能视网膜波是一种在发育中的视网膜神经节细胞（RGCs）之间传播的自发性模式化神经活动，它指导着与活动相关的视图谱的精细化。然而，其启动和潜在机制在很大程度上仍未被揭示。在这里，我们使用幼虫斑马鱼和多种体内方法发现，双极细胞（BCs）负责产生谷氨酸能视网膜波。波起源于 BC 轴突末梢（ATs），并向附近的 BC 侧向传播，向下方的 RGC 和视顶盖垂直传播。其启动是由 BC ATs 的激活和随后的谷氨酸释放触发的，并由这些 AT 上表达的 N-甲基-D-天冬氨酸型谷氨酸受体（NMDARs）介导。BC ATs 上 NMDAR 表达的细胞间不对称性使得波优先在颞侧视网膜启动，那里的 BC ATs 表达更多的 NMDARs。因此，我们的发现表明，谷氨酸能视网膜波是由 BC 通过一个突触前 NMDA 自身受体依赖的过程发起的。
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