Neuronal Plasticity in the Retina

项目摘要/摘要 这项研究项目是一项实验研究，试图了解 神经元网络由于内在昼夜节律的影响而改变或适应 振荡器。最近公布的证据表明，昼夜节律(24小时)时钟在 哺乳动物视网膜调节视杆细胞和视锥细胞对视锥连接的水平细胞的输入 一种二级细胞，通过控制视杆细胞，从视锥细胞接受突触接触。 通过多巴胺D2受体的锥体缝隙连接偶联。初步证据表明 视网膜时钟也调节视杆细胞和视锥细胞的输入，输出 视网膜的神经元。生物钟是一种生物振荡器，具有 持续节律，在没有外部刺激的情况下持续约24小时 定时提示(例如，持续的黑暗)。初步证据表明，视网膜 Clock使用细胞内的信号分子环磷酸腺苷和蛋白激酶A，以及 神经调节剂褪黑素和腺苷，除了多巴胺，调节视杆细胞和 锥体输入到锥体连接的水平细胞和神经节细胞部分通过 含连接蛋白36的缝隙连接。 我们将使用电生理学、神经化学和解剖学技术 确定生物钟是否利用腺苷和褪黑素，以及 细胞内信号分子环磷酸腺苷和蛋白激酶A控制视杆细胞和视锥细胞 锥体和锥体连接的水平细胞的输入部分通过调制连接蛋白36- 包含杆-锥体缝隙接头。我们还将确定时钟是否利用 多巴胺、腺苷和褪黑素控制视杆细胞和视锥细胞的输入 所有的无长突细胞部分通过调节含有连接蛋白36的缝隙连接。那盏灯 兔、小鼠和金鱼视网膜神经元的体外反应和示踪剂偶联 准备工作将在昼夜持续黑暗的条件下进行研究。

Project Summary/Abstract This research project is an experimental study that seeks to understand how neuronal networks change or adapt due to the influence of an intrinsic circadian oscillator. Recent published evidence indicates that a circadian (24-hour) clock in the mammalian retina regulates rod and cone input to cone-connected horizontal cells, a type of second order cell that receives synaptic contact from cones, by controlling rod- cone gap junctional coupling via dopamine D2 receptors. Preliminary evidence suggests that the retinal clock also regulates rod and cone input to ganglion cells, the output neurons of the retina. A circadian clock is a type of biological oscillator that has persistent rhythmicity with a period of approximately 24 hours in the absence of external timing cues (e.g. constant darkness). Preliminary evidence suggests that the retinal clock uses the intracellular signaling molecules cyclic AMP and protein kinase A and the neuromodulators melatonin and adenosine, in addition to dopamine, to regulate rod and cone input to cone-connected horizontal cells and to ganglion cells in part via Connexin36-containing gap junctions. We will use electrophysiological, neurochemical and anatomical techniques to determine whether the circadian clock utilizes adenosine and melatonin, and the intracellular signaling molecules cyclic AMP and protein kinase A to control rod and cone input to cones and cone-connected horizontal cells in part by modulating Connexin36- containing rod-cone gap junctions. We will also determine whether the clock utilizes dopamine, adenosine, and melatonin to control rod and cone input to ganglion cells and AII amacrine cells in part by modulating Connexin36-containing gap junctions. The light responses and tracer coupling of neurons in in vitro rabbit, mouse and goldfish retina preparations will be studied in the day and night under conditions of constant darkness.