Feedback at the photoreceptor synapse is the first neuronal circuit computation in vision, which influences downstream activity patterns within the visual system. Yet, the identity of the feedback signal and the mechanism of synaptic transmission are still not well understood. Here, we combined perturbations of cell-type-specific genes of mouse horizontal cells with two-photon imaging of the result of light-induced feedback in cones and showed that the electrogenic bicarbonate transporter Slc4a5, but not the electroneutral bicarbonate transporter Slc4a3, both expressed specifically in horizontal cells, is necessary for horizontal cell-to-cone feedback. Pharmacological blockage of bicarbonate transporters and buffering pH also abolished the feedback but blocking sodium-proton exchangers and GABA receptors did not. Our work suggests an unconventional mechanism of feedback at the first visual synapse: changes in horizontal cell voltage modulate bicarbonate transport to the cell, via Slc4a5, which leads to the modulation of feedback to cones.

中文翻译：

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钠-碳酸氢盐协同转运蛋白 Slc4a5 介导视觉第一突触的反馈


感光器突触的反馈是视觉中的第一个神经元回路计算，它影响视觉系统内的下游活动模式。然而，反馈信号的身份和突触传递的机制仍然不是很清楚。在这里，我们将小鼠水平细胞的细胞类型特异性基因的扰动与视锥细胞中光诱导反馈结果的双光子成像相结合，并表明电生碳酸氢盐转运蛋白 Slc4a5，而不是电中性碳酸氢盐转运蛋白 Slc4a3，两者都在水平细胞中特异性表达，对于水平细胞到视锥细胞反馈是必需的。碳酸氢盐转运蛋白的药理学阻断和缓冲 pH 值也消除了反馈，但阻断钠-质子交换剂和 GABA 受体没有。我们的工作提出了一种非常规的第一次视觉突触反馈机制：水平细胞电压的变化通过 Slc4a5 调节碳酸氢盐运输到细胞，从而导致对视锥细胞的反馈的调制。