Neural circuits and synapses for early visual processing

用于早期视觉处理的神经回路和突触

• 批准号: 8197368
• 负责人: Jonathan B Demb
• 金额: $ 35.86万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197368
• 关键词: AMPA Receptors; Alpha Cell; Amacrine Cells; Biological; Blindness; Caliber; Cell Death; Cells; Data; Dependence; Development; Eye diseases; Frequencies; Glaucoma; Glutamates; Goals; Inner Plexiform Layer; Interneurons; Ischemia; Kinetics; Lead; Leber' s disease; Ligands; Light; Location; Measures; Mediating; Modeling; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neural Pathways; Neurons; Night Blindness; Output; Pathway interactions; Photoreceptors; Physiological; Process; Property; Prosthesis; Retina; Retinal; Retinal Cone; Retinal Diseases; Role; Signal Transduction; Stratification; Synapses; Testing; Tissues; Trees; Vertebrate Photoreceptors; Vision; Visual; abstracting; base; cell type; desensitization; excitotoxicity; ganglion cell; information processing; neural circuit; presynaptic; receptor; response; retinal rods; visual information; visual process; visual processing; voltage

Abstract: My long-term goal is to understand the biological basis of visual processing at the level of neural circuits and synapses. I am pursuing this goal in the mammalian retina, a tissue comprised of ~70 cell types: ~3-4 photoreceptors (depending on species), ~50 interneurons (horizontal, bipolar and amacrine cells) and ~20 output neurons (ganglion cells). Over the past period, we focused on two types of ganglion cell (ON and OFF Alpha cell) and elucidated fundamental components of their synaptic inputs and mechanisms for contrast adaptation. These accomplishments allow us to now expand our studies to a dozen types of ganglion cell that we recognize based on a combination of functional properties (light-evoked synaptic conductance) and structural properties (dendritic tree diameter and stratification level in the inner plexiform layer). Aim 1 will reveal fundamental circuit mechanisms for night vision, by determining how rod signals are transmitted, via an identified neural pathway, to each ganglion cell type. Rods synapse with rod bipolar cells, which in turn excite the AII amacrine cell; the AII cell signals directly certain ganglion cell types and indirectly others by synapsing with the presynaptic cone bipolar terminal. Preliminary data suggest that a small group of OFF ganglion cell types receives direct AII cell synapses; another group receives indirect synapses, whereas a third group lacks connection to the circuit and loses function in dim light. To encode visual signals in daylight, each ganglion cell type receives glutamatergic synapses from one or more types of cone bipolar cell, but we need to test which ganglion cell types encode glutamate release with an NMDA receptor (Aim 2). Compared to the other major type, AMPA receptors, NMDA receptors have a conductance that is voltage-dependent, lacks desensitization and has relatively slow kinetics. We want to understand the role of NMDA receptors in visual processing, and as a first step we will identify which ganglion cell types express them. For each type, we will test for functional expression by applying NMDA directly; we will test further whether these receptors contribute to high contrast responses under normal physiological conditions. Finally, we will test quantitatively the role of NMDA receptors in visual processing (Aim 3). We will model ligand-gated receptor contributions to contrast responses and test whether NMDA receptors are used preferentially for encoding low versus high contrast. We will test further whether the slow kinetics of the NMDA receptor-mediated response encodes preferentially low temporal frequencies. Proposed studies will yield basic understanding of how retinal circuits and synapses process information and provide background for understanding retinal diseases that either compromise the rod pathway or involve NMDA receptor-mediated excitotoxicity.

摘要：我的长期目标是了解视觉处理的生物学基础 神经回路和突触。我正在哺乳动物视网膜中追求这个目标，该组织由 〜70个细胞类型：〜3-4光感受器（取决于物种），〜50个中间神经元（水平，双极和 无大细胞）和约20个输出神经元（神经节细胞）。在过去的时期，我们专注于两个 神经节细胞的类型（ON和OFF ANPHA细胞）和阐明其基本成分的类型 突触输入和对比度适应的机制。这些成就使我们现在可以 将我们的研究扩展到我们基于组合的十几种类型的神经节细胞 功能特性（轻诱发的突触电导）和结构特性（树突树 内丛状层中的直径和分层水平）。 AIM 1将揭示基本电路 通过确定的神经，通过确定杆信号的传输方式，用于夜视的机制 途径，到每种神经节细胞类型。杆与杆双极细胞突触，进而激发了AII 无大细胞； AII细胞直接信号直接通过某些神经节细胞类型，并间接地通过 与突触前双极末端突触。初步数据表明一小部分 神经节细胞类型接收直接的AII细胞突触；另一组接收间接突触， 而第三组缺乏与电路的连接，并且在昏暗的光中失去了功能。编码Visual 白天的信号，每种神经节细胞类型都会从一种或多种类型的 锥双极细胞，但我们需要测试哪种神经节细胞类型编码谷氨酸 NMDA受体（AIM 2）。与其他主要类型相比，AMPA受体，NMDA受体具有 电压依赖性的电导缺乏脱敏，动力学相对较慢。我们 想了解NMDA受体在视觉处理中的作用，作为第一步，我们将 确定哪种神经节细胞类型表达它们。对于每种类型，我们将测试功能表达式 通过直接应用NMDA；我们将进一步测试这些受体是否有助于高对比度 在正常生理条件下的反应。最后，我们将定量测试NMDA的作用 视觉处理中的受体（AIM 3）。我们将建模配体门控受体贡献以形成对比 响应并测试是否优先使用NMDA受体来编码低与高 对比。我们将进一步测试NMDA受体介导的反应的缓慢动力学 编码优先较低的时间频率。拟议的研究将对 视网膜电路和突触如何处理信息并为理解提供背景 视网膜疾病会损害杆途径或涉及NMDA受体介导的疾病 兴奋性毒性。