Departments of Ophthalmology and Visual Science, Psychological and Brain Sciences, and Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky 40202, USA.
J Neurosci. 2012 Mar 7;32(10):3321-32. doi: 10.1523/JNEUROSCI.5341-11.2012.
In the retina, the receptive fields (RFs) of almost all ganglion cells (GCs) are comprised of an excitatory center and a suppressive surround. The RF center arises from local excitatory bipolar cell (BC) inputs and the surround from lateral inhibitory inputs. Selective antagonists have been used to define the roles of GABA(A) and GABA(C) receptor-mediated input in RF organization. In contrast, the role of glycine receptor (GlyR) subunit-specific inhibition is less clear because the only antagonist, strychnine, blocks all GlyR subunit combinations. We used mice lacking the GlyRα2 (Glra2(-/-)) and GlyRα3 (Glra3(-/-)) subunits, or both (Glra2/3(-/-)), to explore their roles in GC RF organization. By comparing spontaneous and visually evoked responses of WT with Glra2(-/-), Glra3(-/-) and Glra2/3(-/-) ON- and OFF-center GCs, we found that both GlyRα2 and GlyRα3 modulate local RF interactions. In the On pathway, both receptors enhance the excitatory center response; however, the underlying inhibitory mechanisms differ. GlyRα2 participates in crossover inhibition, whereas GlyRα3 mediates serial inhibition. In the Off pathway, GlyRα2 plays a similar role, again using crossover inhibition and enhancing excitatory responses within the RF center. Comparisons of single and double KOs indicate that GlyRα2 and GlyRα3 inhibition are independent and additive, consistent with the finding that they use different inhibitory circuitry. These findings are the first to define GlyR subunit-specific control of visual function and GlyRα2 subunit-specific control of crossover inhibition in the retina.
在视网膜中，几乎所有神经节细胞（GCs）的感受野（RFs）都由一个兴奋中心和一个抑制环绕组成。RF 中心来自局部兴奋双极细胞（BC）输入，而环绕来自侧向抑制输入。选择性拮抗剂已被用于定义 GABA(A)和 GABA(C)受体介导的输入在 RF 组织中的作用。相比之下，甘氨酸受体（GlyR）亚基特异性抑制的作用不太清楚，因为唯一的拮抗剂士的宁阻断了所有 GlyR 亚基组合。我们使用缺乏 GlyRα2（Glra2(-/-)）和 GlyRα3（Glra3(-/-)）亚基或两者（Glra2/3(-/-)）的小鼠来探索它们在 GC RF 组织中的作用。通过比较 WT 与 Glra2(-/-)、Glra3(-/-)和 Glra2/3(-/-)ON-和 OFF-中心 GC 的自发和视觉诱发反应，我们发现 GlyRα2 和 GlyRα3 都调节局部 RF 相互作用。在 ON 通路中，两种受体都增强兴奋中心的反应；然而，潜在的抑制机制不同。GlyRα2 参与交叉抑制，而 GlyRα3 介导串联抑制。在 OFF 通路中，GlyRα2 也发挥类似作用，再次使用交叉抑制并增强 RF 中心内的兴奋反应。单 KO 和双 KO 的比较表明，GlyRα2 和 GlyRα3 的抑制是独立和累加的，这与它们使用不同的抑制回路的发现一致。这些发现首次定义了 GlyR 亚基特异性对视觉功能的控制以及 GlyRα2 亚基特异性对视网膜中的交叉抑制的控制。
