RT Journal Article SR Electronic T1 Dopamine-dependent sensitization of rod bipolar cells by GABA is conveyed through wide-field amacrine cells JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 1994-17 DO 10.1523/JNEUROSCI.1994-17.2017 A1 Amanda M. Travis A1 Stephanie J. Heflin A1 Arlene A. Hirano A1 Nicholas C. Brecha A1 Vadim Y. Arshavsky YR 2017 UL http://www.jneurosci.org/content/early/2017/12/12/JNEUROSCI.1994-17.2017.abstract AB Vertebrate retina has the remarkable ability to support visual function under conditions of limited illumination, including processing 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 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 GABAC 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 GABAC receptor activation required for rod bipolar cell sensitization.Significance Statement: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. Long processes of wide-field amacrine cells span large segments of the retina, which makes them uniquely equipped to normalize and optimize response sensitivity across distant receptive fields and preclude any bias toward local light intensity fluctuations.