Modulation of horizontal cell coupling in the vertebrate retina

脊椎动物视网膜水平细胞耦合的调节

• 批准号: RGPIN-2017-05139
• 负责人: Baldridge, William
• 金额: $ 1.89万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711410
• 关键词: Modulation; horizontal; cell; coupling; vertebrate

The retina is a thin sheet of nerve cells at the back of the eye that converts the light of the visual world into a signal interpretable by the brain. Photoreceptors are the light-sensitive nerve cells of the retina and make connections (synapses) with bipolar cells and horizontal cells (HCs). Bipolar cells make synapses with amacrine cells and ganglion cells, the latter giving rise to processes (axons) that project to the brain as the optic nerve. At the level of the first synapse of the visual system, HCs enhance visual acuity by emphasizing differences in the visual scene. This is economical: the absolute intensity need not be encoded for every point in visual space, only the difference between a point in visual space (called the centre) and the background (called the surround). HCs are thought to contribute to the surround. They are well suited for this being connected to each other by structures called gap junctions that allow electrical coupling. This means that HCs do not act as individual elements but as a sheet of coupled cells. The input they receive from photoreceptors is thus averaged, producing a measure of the background. The coupling of HCs is not static but can be modulated by the level of ambient illumination, suggesting that altering the size and strength of the surround is optimized as a function of ambient illumination level. Several neurochemical modulators, including dopamine, retinoic acid and nitric oxide, have been shown to reduce HC coupling, but when they act endogenously remains uncertain. This research program seeks to understand the modulation of HC coupling in the vertebrate retina using a well-characterized model system, the goldfish. The role of neurochemical modulators, as mediators of the changes of HC coupling produced by altered ambient illumination, will be investigated by recording the light-evoked responses of HCs to determine their receptive-field size (a function of coupling) and by injecting tracers that pass through gap junctions (to assess directly the extent of coupling). Although there are neurons in the retina that could be the source of each neuromodulator, it is also possible that one (dopamine) is, in addition, provided by a non-neuronal source, the retinal pigmented epithelium (RPE). Using a readout of dopamine release in the retina that is easy to measure, light-dependent cone contraction, experiments are proposed to test the hypothesis that the RPE is a source of dopamine that could affect the neural retina. This research program will add to our knowledge of the function of HCs in the vertebrate retina. Although curiosity-driven, basic research, such detailed knowledge of retinal function could ultimately prove useful for the development of retinal prosthesis or to guide machine vision design. The research program also provides several opportunities for undergraduate and graduate training.

视网膜是位于眼睛后部的一层薄薄的神经细胞，它将视觉世界的光线转化为大脑可以解释的信号。光感受器是视网膜的感光神经细胞，并与双极细胞和水平细胞（HC）建立连接（突触）。双极细胞与无长突细胞和神经节细胞形成突触，后者产生突起（轴突），突起作为视神经投射到大脑。在视觉系统的第一突触水平，HC通过强调视觉场景中的差异来增强视敏度。这是经济的：不需要为视觉空间中的每个点编码绝对强度，而只需要为视觉空间中的点（称为中心）和背景（称为环绕）之间的差编码绝对强度。 HC被认为有助于周围环境。它们非常适合通过称为间隙连接的结构彼此连接，该结构允许电耦合。这意味着HC不是作为单独的元素，而是作为一片耦合的细胞。它们从光感受器接收的输入因此被平均，产生背景的测量。HC的耦合不是静态的，而是可以通过环境照明水平来调制，这表明改变环绕的大小和强度作为环境照明水平的函数被优化。几种神经化学调节剂，包括多巴胺，视黄酸和一氧化氮，已被证明可以减少HC偶联，但它们何时内源性起作用仍不确定。 该研究计划旨在使用表征良好的模型系统金鱼来了解脊椎动物视网膜中HC耦合的调节。神经化学调节剂的作用，作为介质的HC耦合的变化所产生的改变环境照明，将通过记录HC的光诱发反应，以确定其感受野的大小（耦合的函数），并通过注射示踪剂，通过间隙连接（直接评估耦合的程度）进行研究。虽然视网膜中存在神经元，其可能是每种神经调节剂的来源，但也可能一种（多巴胺）另外由非神经元来源视网膜色素上皮（RPE）提供。使用易于测量的视网膜中多巴胺释放的读数，光依赖性视锥收缩，提出实验来测试RPE是可能影响神经视网膜的多巴胺来源的假设。 这项研究计划将增加我们对脊椎动物视网膜中HC功能的了解。虽然好奇心驱动的基础研究，这种视网膜功能的详细知识最终可能被证明对视网膜假体的开发或指导机器视觉设计有用。该研究计划还提供了本科生和研究生培训的几个机会。