Neural Circuit Plasticity in the Retina

该研究项目是一项实验性研究，旨在了解神经网络如何改变或 由于视网膜对白天发生的环境光水平的逐渐变化的响应而适应， 夜间，以及视网膜固有的昼夜（24小时）时钟的影响。的发布 视网膜中的神经调节剂多巴胺由视网膜时钟控制，视网膜时钟增加多巴胺水平 足以在黎明时激活视锥细胞上高度敏感的多巴胺D4受体。此外，不同的非- 昼夜节律光响应过程在响应明亮的光时在更大程度上增加多巴胺水平。 中午的光照使锥体双极细胞树突上较不敏感的多巴胺D1受体， 从视锥细胞接受突触输入的二级细胞被激活。 拟议的实验将研究明亮的光诱导的D1受体激活的增加是否 增强水平细胞（另一种接受视锥细胞输入的二级细胞）的GABA信号 通过增强视锥双极细胞树突GABAA受体的功能，使其在白天向视锥双极细胞迁移。的 提出的实验还将研究视网膜时钟是否通过降低D4受体激活， 晚上，通过增强GABAA，加强GABA信号从水平细胞到锥体在夜间在黑暗中 视锥突触末梢的受体功能。将使用兔视网膜切片的电生理记录 研究视锥双极细胞的光反应和GABAA受体活性以及GABA信号转导， 水平细胞到锥状双极细胞。此外，在完整的金鱼和兔神经细胞的电生理记录， 视网膜将用于研究视锥细胞的光反应和GABAA受体活性以及GABA信号传导 从水平细胞到视锥细胞神经化学，细胞/分子和解剖技术也将被采用 使用完整的兔子和鱼视网膜，在昼夜持续黑暗和白天进行研究 在保持照明之后。

This research project is an experimental study that seeks to understand how neuronal networks change or adapt due to the response of the retina to the gradual change in the ambient light level that occurs day and night, and the influence of the circadian (24-h) clock that is intrinsic to the retina. The release of the neuromodulator dopamine in the retina is controlled by the retinal clock, which increases dopamine levels sufficiently at dawn to activate the highly sensitive dopamine D4 receptors on cones. In addition, distinct non- circadian light responsive processes increase dopamine levels to a much greater extent in response to bright illumination at midday so that the less sensitive dopamine D1 receptors on dendrites of cone bipolar cells, a type of second order cell that receives synaptic input from cones, are activated. The proposed experiments will study whether the bright light-induced increase in D1 receptor activation strengthens GABA signaling from horizontal cells (another type of second order cell that receives cone input) to cone bipolar cells in the day by enhancing GABAA receptor function of cone bipolar cell dendrites. The proposed experiments will also investigate whether the retinal clock, by decreasing D4 receptor activation at night, strengthens GABA signaling from horizontal cells to cones at night in the dark by enhancing GABAA receptor function of cone synaptic terminals. Electrophysiological recording in rabbit retinal slices will be used to study the light responses and GABAA receptor activity of cone bipolar cells and GABA signaling from horizontal cells to cone bipolar cells. Also, electrophysiological recording in intact goldfish and rabbit neural retinas will be used to study the light responses and GABAA receptor activity of cones and GABA signaling from horizontal cells to cones. Neurochemical, cell/molecular, and anatomical techniques will also be employed using intact rabbit and fish retinas, studied in the day and night under constant darkness, and in the day following maintained illumination.