NEUROMODULATORY PATHWAYS IN THE RETINA

本提案侧重于对以下内容进行说明： 视网膜中负责调节视觉的神经通路 信号. 例如，作为外层视网膜，视锥细胞的行为是 由视杆细胞活动调节。 视杆细胞和视锥细胞的信号由多巴胺调节。 光感受器和二级细胞之间的增益由横向调制。 未知途径、药理学和机制的相互作用。 在内 从双极细胞到三级细胞的视网膜透射由 反馈到双极细胞通过未知的药理学和功能 机制等 视网膜斑片记录同步染色技术 切片第一次提供了一种定义路径的方法， 确定药理学，表征受体，并测试第二 信使系统，以便可以定义神经调节通路。 突触电流可以被测量，由发射器的喷射引起 物质或跨视网膜电流，激活特定的突触通路 在切片中。 细胞膜可以通过电压的阶跃极化， 发射机和调制器的存在和不存在，同时隔离它们的 对特定电压门控膜电流的影响。 的影响 释放的调节可以通过记录来自 细胞与对象细胞突触后连接，因此使用突触后细胞作为 释放的生物测定 第二信使系统的行为可以 通过将调节剂和阻断剂引入细胞质来控制， 路径电极。 有了这些技术，调节信号的来源，它们的药理学， 膜受体，第二信使途径，以及 可以定义受调制的影响。 这项工作对健康有价值 科学，因为它试图定义一些基本的机制， 潜在的视觉功能。 由于大部分机制是由 在这些研究中定义的药理学， 治疗也将得到明确。 因此，可以提供一种 视网膜功能（或功能障碍）与药理学之间的联系 干预

This proposal focusses on providing a description of the components of neural pathways in the retina responsible for the modulation of visual signals. For example, as the outer retina the behavior of cones is modulated by rod activity. Rod and cone signals are modulated by dopamine. Gain between photoreceptors and second order cells is modulated by lateral interactions of unknown path, pharmacology and mechanism. At the inner retina transmission from bipolar to third order cells is modulated by feedback to bipolar cells via unknown pharmacological and functional mechanisms. The technique of patch recording and simultaneous staining in retinal slices provides for the first time a means for defining pathways, determining pharmacology, characterizing receptors, and testing second messenger systems, so that the neuromodulatory pathways can be defined. Synaptic currents can be measured, elicited by puffs of transmitter substances or transretinal current, activating specific synaptic accessible in the slice. Cell membranes can be polarized by steps of voltage in the presence and absence of transmitters and modulators, while isolating their effects upon specific voltage-gated membrane currents. The effects of modulation of release can be measured by recording synaptic inputs from cells postsynaptic to the subject cell thus using the postsynaptic cell as a bioassay for release. The behavior of second messenger systems can be controlled by introducing modulators and blockers into the cytoplasm via the path electrode. With these techniques the source of modulatory signals, their pharmacology, the membrane receptors, the second messenger pathways, and the sites affected by the modulation can be defined. This work is of value in health science because it attempts to define some of the fundamental mechanisms underlying visual functions. Since much of the mechanism is mediated by pharmacology to be defined in these studies, the route for medical treatment will also be clarified. Thus it may be possible to provide a link between retinal function (or dysfunction) and pharmacological intervention.