At the first retinal synapse, horizontal cells (HCs) contact both photoreceptor terminals and bipolar cell dendrites, modulating information transfer between these two cell types to enhance spatial contrast and mediate color opponency. The synaptic mechanisms through which these modulations occur are still debated. The initial hypothesis of a GABAergic feedback from HCs to cones has been challenged by pharmacological inconsistencies. Surround antagonism has been demonstrated to occur via a modulation of cone calcium channels through ephaptic signaling and pH changes in the synaptic cleft. GABAergic transmission between HCs and cones has been reported in some lower vertebrates, like the turtle and tiger salamander. In these reports, it was revealed that GABA is released from HCs through reverse transport and target GABA receptors are located at the cone terminals. In mammalian retinas, there is growing evidence that HCs can release GABA through conventional vesicular transmission, acting both on autaptic GABA receptors and on receptors expressed at the dendritic tips of the bipolar cells. The presence of GABA receptors on mammalian cone terminals remains equivocal. Here, we looked specifically for functional GABA receptors in mouse photoreceptors by recording in the whole-cell or amphotericin/gramicidin-perforated patch clamp configurations. Cones could be differentiated from rods through morphological criteria. Local GABA applications evoked a Cl− current in cones but not in rods. It was blocked by the GABAA receptor antagonist bicuculline methiodide and unaffected by the GABAC receptor antagonist TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid]. The voltage dependency of the current amplitude was as expected from a direct action of GABA on cone pedicles but not from an indirect modulation of cone currents following the activation of the GABA receptors of HCs. This supports a direct role of GABA released from HCs in the control of cone activity in the mouse retina.

中文翻译：

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小鼠视锥细胞感光器中功能性 GABAA 而非 GABAC 受体的证据

在第一个视网膜突触处，水平细胞 (HC) 接触光感受器末端和双极细胞树突，调节这两种细胞类型之间的信息传递，以增强空间对比度并调节颜色对立性。这些调节发生的突触机制仍然存在争议。从 HC 到视锥细胞的 GABA 能反馈的最初假设受到药理学不一致的挑战。已证明会发生周围拮抗作用通过通过 ephaptic 信号传导和突触间隙中的 pH 变化来调节锥形钙通道。据报道，在一些低等脊椎动物，如龟和虎蝾螈中，HCs 和视锥细胞之间的 GABA 能传递。在这些报告中，揭示了 GABA 通过反向运输从 HCs 中释放出来，目标 GABA 受体位于锥体末端。在哺乳动物视网膜中，越来越多的证据表明 HC 可以通过常规的囊泡传输释放 GABA，同时作用于自体 GABA 受体和双极细胞树突尖端表达的受体。哺乳动物锥体末端 GABA 受体的存在仍然模棱两可。这里，我们通过在全细胞或两性霉素/短杆菌肽穿孔膜片钳配置中记录，专门寻找小鼠光感受器中的功能性 GABA 受体。通过形态学标准可以区分视锥细胞和视杆细胞。本地 GABA 应用引发了一个 Cl-电流在锥体中，但不在杆中。它被 GABA 阻止了一种受体拮抗剂荷包牡丹碱甲硫醚，不受 GABA 影响C受体拮抗剂 TPMPA [(1,2,5,6-四氢吡啶-4-基)甲基次膦酸]。电流幅度的电压依赖性与预期的 GABA 对锥体蒂的直接作用一致，但不是来自 HC 的 GABA 受体激活后锥体电流的间接调节。这支持从 HC 释放的 GABA 在控制小鼠视网膜视锥细胞活动中的直接作用。