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: 7781955
• 负责人: Jonathan B Demb
• 金额: $ 34.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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/7781955
• 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; base; cell type; desensitization; excitotoxicity; ganglion cell; information processing; neural circuit; presynaptic; public health relevance; receptor; response; retinal rods; visual information; visual process; visual processing; voltage

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Proposed studies will provide background for understanding the impact of eye diseases that impair night vision (i.e., retinitis pigmentosa, congenital stationary night blindness) and eye diseases that involve cell death caused by excitotoxicity (i.e., glaucoma, ischemia). Studies will lead to a better understanding of how the retina processes visual information, which could facilitate the development of prosthetic devices for stimulating preserved retinal cells in certain forms of blindness.

描述（由申请人提供）：我的长期目标是了解在神经回路和突触水平上视觉处理的生物学基础。我正在哺乳动物视网膜中追求这一目标，该组织由约70种细胞类型组成：〜3-4光感受器（取决于物种），〜50个中间神经元（水平，双极和双极细胞）和〜20个输出神经元（神经节细胞）。在过去的时期中，我们专注于两种类型的神经节细胞（On和Off Alpha细胞），并阐明了其突触输入的基本成分和用于对比度适应的机制。这些成就使我们现在可以将研究扩展到十几种类型的神经节细胞，我们根据功能特性（光诱发的突触电导率）和结构特性（树突状树直径和内部丛状层中的树突状树直径和分层水平）认识到。 AIM 1将通过确定杆信号如何通过已识别的神经途径传输到每种神经节细胞类型来揭示用于夜视的基本电路机制。杆与杆双极细胞突触，这反过来激发了AII amacrine细胞。 AII细胞通过与突触前双极末端突触直接向某些神经节细胞类型进行信号，并间接地信号。初步数据表明，一小部分OFF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功能。为了在日光中编码视觉信号，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接收谷氨酸能突触，但是我们需要测试哪种神经节细胞类型编码用NMDA受体释放谷氨酸（AIM 2）。与其他主要类型相比，AMPA受体，NMDA受体具有依赖电压的电导，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，我们将通过直接应用NMDA来测试功能表达。我们将进一步测试这些受体在正常生理条件下是否有助于高对比度反应。最后，我们将定量测试NMDA受体在视觉处理中的作用（AIM 3）。我们将对配体门控受体的贡献进行对比反应的贡献，并测试是否优先使用NMDA受体来编码低对比度和高对比度。我们将进一步测试NMDA受体介导的响应的缓慢动力学是否优先编码较低的时间频率。拟议的研究将对视网膜回路和突触如何处理过程信息产生基本了解，并为理解损害杆途径或涉及NMDA受体介导的兴奋性兴奋性的视网膜疾病提供背景。 公共卫生相关性：拟议的研究将为理解造成夜视障碍的影响（即色素性视网膜炎，先天性夜间夜间失明）和眼部疾病的影响提供背景，这些眼睛涉及受兴奋性毒性引起的细胞死亡（即，glaucoma，缺血，缺血）。研究将使您更好地理解视网膜如何处理视觉信息，这可能有助于开发以某些形式的失明形式刺激保留的视网膜细胞的假体设备。