Retinal Synaptic Transmission: Channels and Transmitters

描述（由申请人提供）：视觉的重要特征之一 视网膜中的信息处理是相对持续的 外视网膜的光反应更多样化的反应，包括 在视网膜内层形成短暂的反应。增加 有证据表明双极细胞在视网膜处理过程中起着积极的作用 而内层视网膜的多样化反应部分源于 双极细胞释放不同形式的递质。仗着什么 产生不同形式的发射器释放的机制， 双极细胞处理在多大程度上影响了整个视网膜 处理仍有待阐明。这项建议的长远目标是 了解电压依赖性膜通道在双极细胞中的作用 信号处理哺乳动物视网膜双极细胞表达多种 电压依赖性通道，包括低电压激活（LVA）和 轴突末端的高电压激活（HVA）Ca 2+通道， 锥双极细胞亚群中的电压门控Na+通道。生理 多个电压激活的Ca 2+通道和电压门控Na+的作用 将研究双极细胞信号处理中的通道。第一部分 研究LVA和L-型HVA钙通道在 双极细胞递质释放。具体目标1将确定Ca 2 + 位于轴突终末并参与传递的通道类型 释放不同亚型的双极细胞。具体目标2将决定 双极细胞释放递质的时间特性 激活LVA和L型Ca 2+通道。本申请的第二部分 研究电压依赖性膜通道在形成双极 细胞反应波形。具体目标3将确定不同的 自发和诱发反应波形中的电压依赖性通道， 孤立的双极细胞。具体目标4将确定双相情感障碍的亚型 表达Na+通道的细胞和Na+电流的贡献 细胞光响应波形。这些研究将用分离的 哺乳动物视网膜切片制备中的双极细胞和双极细胞 视网膜膜片钳记录和光学Ca 2+成像方法将在 就业。我们从这些研究中获得的知识将导致更好的 了解哺乳动物视网膜的基本视觉信息处理。 电压激活钙通道在突触中作用的认识 传播也可以为确定疾病的机制提供见解 是由突触功能障碍引起的

DESCRIPTION (provided by applicant): One of the important features of visual information processing in the retina is the conversion of relatively sustained light responses in the outer retina to more diversified responses, including the formation of the transient response, in the inner retina. Increasing evidence suggests that bipolar cells play an active role in retinal processing and that the diversified responses in the inner retina originate, in part, by means of the different forms of transmitter release from bipolar cells. By what mechanism(s) the different forms of transmitter release are generated and to what extent bipolar cell processing contributes to the overall retinal processing remain to be elucidated. The long-term objective of this proposal is to understand the roles of voltage-dependent membrane channels in bipolar cell signal processing. Mammalian retinal bipolar cells express a variety of voltage-dependent channels, including low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca2+ channels at the axon terminals and voltage-gated Na+ channels in a subset of cone bipolar cells. The physiological roles of multiple voltage-activated Ca2+ channels and voltage-gated Na+ channels in bipolar cell signal processing will be investigated. The first part of this proposal is to study the roles of LVA and L-type HVA Ca2+ channels in bipolar cell transmitter release. Specific aim 1 will determine the Ca2+ channel type(s) located at the axon terminals and involved in transmitter release of different subtypes of bipolar cells. Specific aim 2 will determine the temporal properties of transmitter release from bipolar cells during the activation of LVA and L-type Ca2+ channels. The second part of this application is to study the roles of voltage-dependent membrane channels in shaping bipolar cell response waveforms. Specific aim 3 will determine the roles of different voltage-dependent channels in the spontaneous and evoked response waveforms in isolated bipolar cells. Specific aim 4 will determine the subtypes of bipolar cells expressing Na+ channels and the contribution of Na+ currents in bipolar cell light response waveforms. The studies will be carried out with isolated bipolar cells and with bipolar cells in retinal slice preparations of mammalian retinas. Patch-clamp recording and optical Ca2+ imaging methods will be employed. The knowledge we gain from these studies will lead to a better understanding of basic visual information processing in the mammalian retina. The understanding of the role of voltage-activated Ca2+ channels in synaptic transmission may also provide insight for identifying the mechanism of diseases caused by synaptic dysfunction.