Light and dark adaptation in the primate retina

灵长类动物视网膜的明暗适应

• 批准号: 6233359
• 负责人: DAVID W MARSHAK
• 金额: $ 19.39万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-25 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233359
• 关键词: amacrine cells; animal data; computational neuroscience; dopamine; human data; mathematical model; membrane potentials; model design /development; retinal adaptation

The visual system remains responsive over an enormous range of ambient illumination, and this adaptation is accomplished entirely within the retina. While some of these changes in sensitivity are mediated by the rods and cones, themselves, there are also important contributions to adaptation from the other neurons in the retina. Dopamine will be the focus in the first grant period because it is thought to play a critical role in light adaptation, changing the strength of chemical and electrical synapses so that the retina remains sensitive to contrast as the intensity of the background light increases. The major targets of the dopaminergic neurons in mammals, All amacrine cells are known to be uncoupled both by dopamine and b photopic light stimulation. However, it is still uncertain which other effects of light are attributable to dopamine in mammalian retinas and what role, if any, dopamine plays in dark adaptation. Last year, the membrane properties of dopaminergic neurons were described for the first time, and they were found to fire action potentials spontaneously in vitro. Two other surprising, new findings were that, in total darkness, All amacrine cells are uncoupled and dopamine is released from the retina. These data led to the hypothesis that dopaminergic neurons are spontaneously active in total darkness, tonically inhibited in scotopic backgrounds and receive both excitatory and inhibitory input in brighter background. The goal of the proposed experiments is to test elements of this hypothesis more rigorously using computer models. It is clear that dopaminergic retinal neurons pla an important role in human vision since the electroretinogram is abnormal in patients with Parkinson's disease, in which dopaminergic neurons degenerate, and in patients taking neuroleptic drugs that block dopamine receptors. The results of these experiments may also be applicable to dopaminergic neurons elsewhere in the Central nervous system. For example, the effect of dopamine on electrical coupling was discovered in the retina and later found to occur in the brain, as well.

视觉系统在巨大的环境照明范围内保持响应，并且这种适应完全在视网膜内完成。虽然这些敏感性的变化中有一些是由视杆细胞和视锥细胞本身介导的，但视网膜中的其他神经元也对适应做出了重要贡献。多巴胺将成为第一个资助期的焦点，因为它被认为在光适应中起着关键作用，改变化学和电突触的强度，使视网膜在背景光强度增加时对对比度保持敏感。无长突细胞是哺乳动物多巴胺能神经元的主要作用靶细胞，在多巴胺和B明视光刺激下，无长突细胞均发生解偶联。然而，仍然不确定的是，哺乳动物视网膜中的多巴胺对光的其他影响以及多巴胺在暗适应中的作用（如果有的话）。去年，多巴胺能神经元的膜特性首次被描述，并且发现它们在体外自发地激发动作电位。另外两个令人惊讶的新发现是，在完全黑暗的情况下，所有的无长突细胞都是分开的，多巴胺从视网膜中释放出来。这些数据导致的假设，多巴胺能神经元自发地活跃在完全黑暗中，紧张性抑制在暗视背景和接受兴奋性和抑制性输入在较亮的背景。拟议实验的目标是使用计算机模型更严格地测试这一假设的要素。显然，多巴胺能视网膜神经元在人类视觉中发挥重要作用，因为帕金森病患者的视网膜电图异常，其中多巴胺能神经元退化，并且在服用阻断多巴胺受体的神经安定药物的患者中。这些实验的结果也可能适用于中枢神经系统其他部位的多巴胺能神经元。例如，多巴胺对电耦合的影响是在视网膜中发现的，后来发现也发生在大脑中。