Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina
Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina
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DOI：
10.1523/jneurosci.0442-12.2012
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发表时间：
2012-08-01
影响因子：
5.3
通讯作者：
Janssen-Bienhold, Ulrike
中科院分区：
文献类型：
--
作者：
Sonntag, Stephan;Dedek, Karin;Janssen-Bienhold, Ulrike
在大脑中，包括视网膜，中间神经元显示出巨大的结构和功能多样性。视网膜水平细胞代表一类与光感受器和ON双极细胞形成三联体突触的中间神经元。在第一个视网膜突触处，水平细胞通过反馈和前馈抑制来调节从光感受器到双极细胞的信号传输。为了测试完全发育的视网膜如何对水平细胞的特定损失作出反应，使用白喉毒素（DT）/DT-受体系统和连接蛋白57启动子从成年小鼠特异性地消融这些中间神经元。消融后，视网膜网络广泛的重塑：杆收回外丛状层的轴突和部分退化，而锥存活。锥蒂保留在外丛状层和保存突触接触关闭，但不与ON双极细胞。因此，视网膜ON通路受损，导致视网膜电图振幅降低和潜伏期延长。然而，神经节细胞的反应显示只有轻微的变化，在时间过程中，大概是因为ON双极细胞形成多个异位突触与光感受器，和视觉性能，评估与optomotor系统，只有轻微的影响。因此，整个中间神经元类的损失甚至可以通过成人视网膜网络在很大程度上得到补偿。
In the brain, including the retina, interneurons show an enormous structural and functional diversity. Retinal horizontal cells represent a class of interneurons that form triad synapses with photoreceptors and ON bipolar cells. At this first retinal synapse, horizontal cells modulate signal transmission from photoreceptors to bipolar cells by feedback and feedforward inhibition. To test how the fully developed retina reacts to the specific loss of horizontal cells, these interneurons were specifically ablated from adult mice using the diphtheria toxin (DT)/DT-receptor system and the connexin57 promoter. Following ablation, the retinal network responded with extensive remodeling: rods retracted their axons from the outer plexiform layer and partially degenerated, whereas cones survived. Cone pedicles remained in the outer plexiform layer and preserved synaptic contacts with OFF but not with ON bipolar cells. Consistently, the retinal ON pathway was impaired, leading to reduced amplitudes and prolonged latencies in electroretinograms. However, ganglion cell responses showed only slight changes in time course, presumably because ON bipolar cells formed multiple ectopic synapses with photoreceptors, and visual performance, assessed with an optomotor system, was only mildly affected. Thus, the loss of an entire interneuron class can be largely compensated even by the adult retinal network.