NEUROMODULATORY PATHWAYS IN THE RETINA

本建议书重点介绍以下组件： 视网膜中负责视觉调节的神经通路 信号。例如，作为外层视网膜，视锥细胞的行为是 受杆状活动的调节。视杆和视锥信号是由多巴胺调制的。 光感受器和二阶细胞之间的增益由侧向调制 未知途径、药理和机制的相互作用。在内心深处 视网膜从双极细胞到三级细胞的传递受 通过未知的药理和功能反馈给双极细胞 机械装置。 视网膜斑片记录与同步染色技术 切片首次提供了定义路径的手段， 确定药理，确定受体特征，并测试第二次 信使系统，这样就可以定义神经调节通路。 突触电流可以被测量，由传输器的喷雾引起 物质或跨视网膜电流，激活特定突触可及 在切片中。细胞膜可以通过电压的阶跃来极化 发射机和调制器的存在和不存在，同时隔离其 对特定电压门控膜电流的影响。的影响 释放的调制可以通过记录突触输入来测量 突触后细胞与目标细胞发生突触，从而将突触后细胞用作 一种释放的生物测定法。第二信使系统的行为可以是 通过将调节剂和阻断剂引入细胞质来控制的 路径电极。 有了这些技术，调制信号的来源，它们的药理， 膜受体、第二信使通路和部位 受调制的影响可以定义。这项工作对健康很有价值 科学，因为它试图定义一些基本的机制 潜在的视觉功能。因为大部分的机制是由 药理学在这些研究中被定义，医学的路线 治疗方法也将得到澄清。因此，有可能提供一个 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.