Retinal Synaptic Transmission: Channels and Transmitters

描述(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转换 外视网膜对更多样化的反应的光反应，包括 在视网膜内部形成的瞬变反应。渐增 有证据表明，双极细胞在视网膜加工中起着积极的作用 而视网膜内部的不同反应部分源于 从双极细胞释放不同形式的递质的方式。凭什么？ 机制(S)不同形式的发射器释放是产生和 双极细胞处理在多大程度上影响整个视网膜 其加工过程尚待阐明。这项提议的长期目标是 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 电压依赖通道，包括低压激活(LVA)和 轴突终末的高压激活(HVA)钙通道 锥体双极细胞子集的电压门控Na+通道。生理学 多个电压激活的钙通道和电压门控性钠离子的作用 我们将研究双极电池信号处理中的通道。第一部分 本研究的目的是研究LVA和L型HVA钙通道在心肌梗死中的作用。 双极电池发射机释放。特定目标1将决定钙离子 通道型(S)，位于轴突终末，参与递质 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 LVA和L型钙通道的激活。此应用程序的第二部分 是研究电压依赖的膜通道在形成双极中的作用 细胞反应波形。具体目标3将确定不同的角色 自发性反应和诱发反应波形中的电压依赖性通道 分离的双极细胞。具体目标4将确定双相情感障碍的亚型 表达Na+通道的细胞及其在双极活动中的作用 细胞光响应波形。研究将在隔离的情况下进行 哺乳动物视网膜切片制备中的双极细胞及其与双极细胞的关系 视网膜。膜片钳记录和光学钙成像方法将是 受雇的。我们从这些研究中获得的知识将导致更好的 哺乳动物视网膜中基本视觉信息处理的理解。 电压激活钙通道在突触中作用的认识 传播也可能为识别疾病的机制提供洞察力 由突触功能障碍引起。

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.