Development of function in the vertebrate retina

脊椎动物视网膜功能的发育

• 批准号: 6544950
• 负责人: JUAN IGAL KORENBROT
• 金额: $ 35.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6544950
• 关键词: acetylcholine; alternatives to animals in research; biological signal transduction; biophysics; calcium ion; developmental neurobiology; electrophysiology; fluorescence microscopy; gamma aminobutyrate; ganglion cell; glutamates; glycine; ion transport; membrane channels; neuroanatomy; neurogenesis; neuropharmacology; organ culture; photostimulus; retina; single cell analysis; synapses; tissue /cell preparation; trout /salmon; voltage /patch clamp

DESCRIPTION (provided by applicant): The goal of this research program is to further our understanding of the developmental maturation of functional networks in the vertebrate retina, and to investigate the signaling cascades that direct and control this maturation. In particular, we propose to test the thesis that neural activity is a signal that helps sculpt intricate, mature circuits in the retina from initially imprecise neuronal connections. To achieve this goal, first, the maturation of the retinal network in the peripheral growth zone of the fish retina will be characterized. In this zone, at the rim of the mature tissue, new retina develops continuously in a process similar, if not identical, to embryological development. Fish offer an experimental model accessible to manipulations not readily possible in the mammalian eye. To characterize circuitry maturation, the electrophysiological properties of ganglion cells, the output neuron of the retina, will be investigated. Developmental changes in both the intrinsic properties of individual ganglion cells and in the retinal network reflected, in turn, in ganglion cell function will be studied. Maturation of neural circuits will be studied through measurements of the spiking activity of developing ganglion cells. The neural networks formed after photoreceptors have matured will be investigated by characterizing the development of the functional properties of light-driven networks. Maturation of the intrinsic electrophysiological properties of developing ganglion cells will be studied through measurements of the biophysical and pharmacological properties of ligand-gated membrane currents in single cells. After defining the features of network maturation, we will assess the role of neural activity as a modulator of maturation by testing the effects on network maturation of blocking specific synaptic activity-dependent signaling pathways.

描述（由申请人提供）：该研究计划的目标是进一步了解脊椎动物视网膜功能网络的发育成熟，并研究指导和控制这种成熟的信号级联。特别是，我们建议测试这样的论点：神经活动是一种信号，有助于从最初不精确的神经元连接中塑造出视网膜中复杂、成熟的电路。为了实现这一目标，首先，将表征鱼视网膜外围生长区视网膜网络的成熟。在这个区域，在成熟组织的边缘，新的视网膜不断发育，其过程与胚胎发育相似，甚至完全相同。鱼类提供了一种实验模型，可以进行哺乳动物眼睛无法轻易进行的操作。 为了表征电路成熟，将研究神经节细胞（视网膜的输出神经元）的电生理特性。将研究单个神经节细胞的内在特性和反过来反映在神经节细胞功能中的视网膜网络的发育变化。将通过测量发育中的神经节细胞的尖峰活动来研究神经回路的成熟。将通过表征光驱动网络功能特性的发展来研究光感受器成熟后形成的神经网络。将通过测量单细胞中配体门控膜电流的生物物理和药理学特性来研究发育中的神经节细胞的内在电生理特性的成熟。 在定义了网络成熟的特征后，我们将通过测试阻断特定突触活动依赖性信号通路对网络成熟的影响来评估神经活动作为成熟调节剂的作用。