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）：该研究计划的目的是进一步了解脊椎动物视网膜功能网络的发展成熟，并调查直接和控制这种成熟的信号级联。特别是，我们建议检验以下论点：神经活动是一个信号，该信号有助于视网膜中最初不精确的神经元连接中复杂的成熟电路。为了实现这一目标，首先将表征视网膜外围生长区域中视网膜网络的成熟。在该区域，在成熟组织的边缘，新的视网膜在与胚胎学发展相似的过程中连续发展。鱼提供了一种实验模型，可以在哺乳动物眼中不容易访问操作。 为了表征电路成熟，将研究神经节细胞的电生理特性，即视网膜的输出神经元。将研究神经节细胞的内在特性以及在神经节细胞功能中反映的视网膜网络中的发育变化。通过测量发育中的神经节细胞的尖峰活性，将研究神经回路的成熟。在光感受器成熟后形成的神经网络将通过表征光驱动网络的功能性能的发展来研究。通过测量单个细胞中配体门控膜电流的生物物理和药理特性，将研究发育中神经节细胞的内在电生理特性的成熟。 定义网络成熟的特征后，我们将通过测试阻止特定突触活动依赖性信号通路的网络成熟的影响来评估神经活动作为成熟的调节剂的作用。