Department of Pharmacology and.
Department of Ophthalmology, Duke University, Durham, North Carolina 27710.
J Neurosci. 2018 Jan 17;38(3):723-732. doi: 10.1523/JNEUROSCI.1994-17.2017. Epub 2017 Dec 7.
The vertebrate retina has the remarkable ability to support visual function under conditions of limited illumination, including the processing of signals evoked by single photons. Dim-light vision is regulated by several adaptive mechanisms. The mechanism explored in this study is responsible for increasing the light sensitivity and operational range of rod bipolar cells, the retinal neurons operating immediately downstream of rod photoreceptors. This sensitization is achieved through the sustained dopamine-dependent GABA release from other retinal neurons. Our goals were to identify the cell type responsible for the GABA release and the site of its modulation by dopamine. Previous studies have suggested the involvement of amacrine and/or horizontal cells. We now demonstrate, using mice of both sexes, that horizontal cells do not participate in this mechanism. Instead, sustained GABA input is provided by a subpopulation of wide-field amacrine cells, which stimulate the GABA receptors at rod bipolar cell axons. We also found that dopamine does not act directly on either of these cells. Rather, it suppresses inhibition imposed on these wide-field cells by another subpopulation of upstream GABAergic amacrine cells, thereby sustaining the GABA receptor activation required for rod bipolar cell sensitization. The vertebrate retina has an exquisite ability to adjust information processing to ever-changing conditions of ambient illumination, from bright sunlight to single-photon counting under dim starlight. Operation under each of these functional regimes requires an engagement of specific adaptation mechanisms. Here, we describe a mechanism optimizing the performance of the dim-light channel of vision, which consists of sensitizing rod bipolar cells by a sustained GABAergic input originating from a population of wide-field amacrine cells. Wide-field amacrine cells span large segments of the retina, making them uniquely equipped to normalize and optimize response sensitivity across distant receptive fields and preclude any bias toward local light-intensity fluctuations.
脊椎动物的视网膜具有在有限光照条件下支持视觉功能的非凡能力，包括处理由单个光子引发的信号。暗视力受几种适应机制的调节。本研究探索的机制负责增加视杆双极细胞的光敏感性和工作范围，视杆双极细胞是视网膜神经元中直接位于视杆感光细胞下游的细胞。这种敏化是通过其他视网膜神经元持续释放多巴胺依赖性 GABA 来实现的。我们的目标是确定负责 GABA 释放的细胞类型及其被多巴胺调制的部位。先前的研究表明，该机制涉及无长突细胞和/或水平细胞。我们现在使用雌雄小鼠证明，水平细胞不参与该机制。相反，持续的 GABA 输入是由一个宽场无长突细胞亚群提供的，该亚群刺激视杆双极细胞轴突上的 GABA 受体。我们还发现，多巴胺不是直接作用于这些细胞中的任何一个。相反，它抑制了另一群上游 GABA 能无长突细胞对这些宽场细胞的抑制作用，从而维持了视杆双极细胞敏化所需的 GABA 受体激活。脊椎动物的视网膜具有一种精妙的能力，可以根据环境光照的不断变化来调整信息处理，从明亮的阳光到昏暗星光下的单光子计数。在这些功能状态下的每一种操作都需要特定的适应机制的参与。在这里，我们描述了一种优化视觉暗光通道性能的机制，该机制通过源自宽场无长突细胞群体的持续 GABA 能输入来敏化视杆双极细胞。宽场无长突细胞跨越视网膜的大段，使它们具有独特的能力，可以在远距离感受野中归一化和优化响应灵敏度，并防止任何偏向于局部光强波动的情况。
