PLASTICITY AND REGENERATION OF RETINAL SYNAPSES

描述（改编自申请人的摘要）：感光细胞是 受到各种遗传疾病和创伤的影响。 其外 节和突触末端对这些病理条件作出反应。 这项建议探讨了感光带突触的可塑性 其再生能力，并具有以下目的：（1）本地化 视杆细胞和视锥细胞中的钙通道;（2）检测是否 突触可塑性受钙信号和囊泡再循环控制; 以及（3）检查成年神经元之间的抑制性相互作用， 限制突触功能的再生和恢复。 共聚焦激光 扫描和电子显微镜将用于分离的光感受器， 与荧光二氢吡啶、蛋白质抑制剂的联合 合成和细胞器的标记，以检查结构可塑性。 通过显微操作在培养物中产生视网膜神经元群 光学镊子，然后是传统的和视频延时显微镜， 将测试潜在的排斥和吸引细胞介导的力量， 再生 这些项目探索了轴突参与的可能机制， 视网膜脱离和视网膜炎中的回缩和神经炎生长 pigmentosa。 了解丝带的细胞生物学 突触可能有助于恢复或保持视网膜正常神经传递 疾病

DESCRIPTION (Adapted from applicant's abstract): The photoreceptor cell is affected by a variety of genetic diseases and trauma. Both its outer segment and the synaptic terminal respond to these pathological conditions. This proposal examines the plasticity of the photoreceptor ribbon synapse and its ability to regenerate and has the following aims: (1) to localize the calcium channels in the rod and cone photoreceptor; (2) to test whether synaptic plasticity is controlled by calcium signals and vesicle recycling; and (3) to examine for inhibitory interaction between adult neurons that may limit regeneration and recovery of synaptic function. Confocal laser scanning and electron microscopy will be used on isolated photoreceptors in conjunction with fluorescent dihydropyridines, inhibitors of protein synthesis, and markers of cell organelles, to examine structural plasticity. Creation of groups of retinal neurons in culture by micromanipulation with optical tweezers, followed by conventional and video time-lapse microscopy, will test potential repulsive and attractant cell-mediated forces during regeneration. The projects explore possible mechanisms involved in axonal retraction and neuritic outgrowth seen in retinal detachment and retinitis pigmentosa, respectively. Understanding the cell biology of the ribbon synapse may help restore or preserve normal neurotransmission in retinal disease.