Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany; Center for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, 72076 Tübingen, Germany.
Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany; Center for Integrative Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, 72076 Tübingen, Germany; Bernstein Center for Computational Neuroscience, University of Tübingen, 72076 Tübingen, Germany.
Curr Biol. 2017 Dec 4;27(23):3603-3615.e5. doi: 10.1016/j.cub.2017.10.050. Epub 2017 Nov 22.
The mouse retina contains a single type of horizontal cell, a GABAergic interneuron that samples from all cone photoreceptors within reach and modulates their glutamatergic output via parallel feedback mechanisms. Because horizontal cells form an electrically coupled network, they have been implicated in global signal processing, such as large-scale contrast enhancement. Recently, it has been proposed that horizontal cells can also act locally at the level of individual cone photoreceptors. To test this possibility physiologically, we used two-photon microscopy to record light stimulus-evoked Ca signals in cone axon terminals and horizontal cell dendrites as well as glutamate release in the outer plexiform layer. By selectively stimulating the two mouse cone opsins with green and UV light, we assessed whether signals from individual cones remain isolated within horizontal cell dendritic tips or whether they spread across the dendritic arbor. Consistent with the mouse's opsin expression gradient, we found that the Ca signals recorded from dendrites of dorsal horizontal cells were dominated by M-opsin and those of ventral horizontal cells by S-opsin activation. The signals measured in neighboring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing. Rather, our experimental data and results from biophysically realistic modeling support the idea that horizontal cells can process cone input locally, extending the classical view of horizontal cell function. Pharmacologically removing horizontal cells from the circuitry reduced the sensitivity of the cone signal to low frequencies, suggesting that local horizontal cell feedback shapes the temporal properties of cone output.
小鼠视网膜包含一种单一类型的水平细胞，即 GABA 能中间神经元，它从可及范围内的所有视锥光感受器中取样，并通过平行的反馈机制调节它们的谷氨酸能输出。由于水平细胞形成电耦合网络，它们已被牵涉到全局信号处理中，例如大规模对比度增强。最近，有人提出水平细胞也可以在单个视锥光感受器水平上发挥局部作用。为了在生理上验证这种可能性，我们使用双光子显微镜记录了视锥轴突末梢和水平细胞树突中的光刺激诱发的 Ca 信号以及外丛状层中的谷氨酸释放。通过用绿光和紫外光选择性地刺激两种小鼠视蛋白，我们评估了来自单个视锥的信号是否仍然在水平细胞树突末梢内孤立，或者它们是否在树突分支中传播。与小鼠视蛋白表达梯度一致，我们发现来自背侧水平细胞树突的记录信号主要由 M-视蛋白激活，而来自腹侧水平细胞的信号则由 S-视蛋白激活。在相邻水平细胞树突末梢中测量的信号在其色觉偏好上差异显著，这表明不存在全局处理。相反，我们的实验数据和生物物理现实建模的结果支持了水平细胞可以局部处理视锥输入的观点，扩展了水平细胞功能的经典观点。药理学上从电路中去除水平细胞会降低视锥信号对低频的敏感性，这表明局部水平细胞反馈会影响视锥输出的时间特性。
