Vertebrate vision begins with light absorption by rod and cone photoreceptors, which transmit signals from their synaptic terminals to second-order neurons: bipolar and horizontal cells. In mouse rods, there is a single presynaptic ribbon-type active zone at which the release of glutamate occurs tonically in the dark. This tonic glutamatergic signaling requires continuous exo- and endocytosis of synaptic vesicles. At conventional synapses, endocytosis commonly requires dynamins: GTPases encoded by three genes (Dnm1–3), which perform membrane scission. Disrupting endocytosis by dynamin deletions impairs transmission at conventional synapses, but the impact of disrupting endocytosis and the role(s) of specific dynamin isoforms at rod ribbon synapses are understood incompletely. Here, we used cell-specific knock-outs (KOs) of the neuron-specific Dnm1 and Dnm3 to investigate the functional roles of dynamin isoforms in rod photoreceptors in mice of either sex. Analysis of synaptic protein expression, synapse ultrastructure, and retinal function via electroretinograms (ERGs) showed that dynamins 1 and 3 act redundantly and are essential for supporting the structural and functional integrity of rod ribbon synapses. Single Dnm3 KO showed no phenotype, and single Dnm1 KO only modestly reduced synaptic vesicle density without affecting vesicle size and overall synapse integrity, whereas double Dnm1/Dnm3 KO impaired vesicle endocytosis profoundly, causing enlarged vesicles, reduced vesicle density, reduced ERG responses, synaptic terminal degeneration, and disassembly and degeneration of postsynaptic processes. Concurrently, cone function remained intact. These results show the fundamental redundancy of dynamins 1 and 3 in regulating the structure and function of rod ribbon synapses.

脊椎动物的视觉始于视杆细胞和视锥细胞光感受器的光吸收，这些光感受器将信号从突触末端传输到二级神经元：双极细胞和水平细胞。在小鼠视杆细胞中，有一个突触前带状活性区，在黑暗中，谷氨酸的释放会在该区进行。这种强直性谷氨酸信号传导需要突触小泡的连续外吞和内吞作用。在传统突触中，内吞作用通常需要动力蛋白：由三个基因 ( Dnm1-3 ) 编码的 GTP 酶，执行膜断裂。通过动力缺失破坏内吞作用会损害传统突触的传递，但破坏内吞作用的影响以及杆带突触中特定动力亚型的作用尚不完全了解。在这里，我们使用神经元特异性Dnm1和Dnm3的细胞特异性敲除 (KO) 来研究动力亚型在任一性别小鼠视杆光感受器中的功能作用。通过视网膜电图 (ERG) 对突触蛋白表达、突触超微结构和视网膜功能的分析表明，动力蛋白 1 和 3 的作用是冗余的，对于支持杆带突触的结构和功能完整性至关重要。单个Dnm3 KO 没有表现出表型，单个Dnm1 KO 仅适度降低突触小泡密度，而不影响囊泡大小和整体突触完整性，而双Dnm1/Dnm3 KO 严重损害囊泡内吞作用，导致囊泡增大、囊泡密度降低、ERG 反应降低、突触终末变性以及突触后过程的分解和变性。同时，视锥细胞功能保持完整。 这些结果表明动力蛋白 1 和 3 在调节杆带突触的结构和功能方面具有基本的冗余性。