Thoreson Wallace B, Sladek Asia L, Barta Cody L, Townsend Lou E
Truhlsen Eye Institute and Department of Ophthalmology and Visual Sciences
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68106.
eNeuro. 2025 Jun 6;12(6). doi: 10.1523/ENEURO.0427-24.2025. Print 2025 Jun.
Rod and cone photoreceptor cells selectively contact different compartments of axon-bearing retinal horizontal cells in the mammalian retina. Cones synapse exclusively on the soma whereas rods synapse exclusively on a large axon terminal compartment. The possibility that rod signals can travel down the axon from terminal to soma has been proposed as a means of producing spectrally opponent interactions between rods and cones, but there is conflicting data about whether this actually occurs. The spectral overlap between rods and cones in mouse makes it difficult to stimulate rod and cone pigments separately. We therefore used optogenetic techniques to analyze photoreceptor inputs into horizontal somas by selectively expressing channelrhodopsin in rods and/or cones. Optogenetic stimulation of rods and cones both evoked large fast inward currents in horizontal cell somas. Cone-driven responses were abolished by eliminating synaptic release in a cone-specific knock-out of the exocytotic calcium sensor, synaptotagmin 1 (Syt1). However, rod-driven responses in horizontal somas were unchanged after eliminating synaptic release from rods but abolished by eliminating release from both rods and cones. This suggests that release from cones is required for transmission of rod signals to horizontal cell somas. Rods and cones are coupled by Cx36 gap junctions, and we found that selective elimination of Cx36 from rods also abolished rod-driven optogenetic responses in horizontal cell somas. Together, these results show that rod signals reach the somas of B-type horizontal cells exclusively via gap junctions with cones and not by transmission down the axon from the axon terminal.
在哺乳动物视网膜中，视杆和视锥光感受器细胞选择性地与带有轴突的视网膜水平细胞的不同部分相接触。视锥仅与胞体形成突触，而视杆仅与一个大的轴突终末部分形成突触。有人提出视杆信号可以从终末沿着轴突向下传至胞体，作为在视杆和视锥之间产生光谱拮抗相互作用的一种方式，但关于这种情况是否实际发生，存在相互矛盾的数据。小鼠视杆和视锥之间的光谱重叠使得难以分别刺激视杆和视锥色素。因此，我们使用光遗传学技术，通过在视杆和/或视锥中选择性表达通道视紫红质来分析光感受器对水平细胞胞体的输入。对视杆和视锥的光遗传学刺激均在水平细胞胞体中诱发了大的快速内向电流。通过在视锥特异性敲除胞吐钙传感器突触结合蛋白1（Syt1）来消除突触释放，可消除视锥驱动的反应。然而，消除视杆的突触释放后，水平细胞胞体中的视杆驱动反应未改变，但同时消除视杆和视锥的释放则可消除该反应。这表明视锥的释放是视杆信号传递至水平细胞胞体所必需的。视杆和视锥通过Cx36缝隙连接相连，我们发现从视杆中选择性消除Cx36也消除了水平细胞胞体中视杆驱动的光遗传学反应。总之，这些结果表明，视杆信号仅通过与视锥的缝隙连接到达B型水平细胞的胞体，而不是通过从轴突终末沿着轴突向下传递。
