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Mechanisms, functions and utility of RGC oscillation in retinal deafferentation mouse models

视网膜传入神经阻滞小鼠模型中 RGC 振荡的机制、功能和效用

基本信息

批准号：
9767210
负责人：
Ching-Kang Jason Chen
金额：
$ 39.63万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-30 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767210
关键词：
Adult Affect Aging Amacrine Cells Axon Biological Process Brain Cells Characteristics Cone Coupled Coupling Deafferentation procedure Development Electroretinography Ensure Exhibits Eye Foundations Future Gap Junctions Genes Glutamate Receptor Glutamates Goals Immunologic Markers Individual Investigation Ipsilateral Kinetics Knock-out Knowledge Light Light Cell Maintenance Masks Mediating Membrane Membrane Potentials Modeling Morphology Mus Night Blindness Outcome Photoreceptors Physiological Potassium Channel Predisposition Property Resources Rest Retina Retinal Retinal Degeneration Retinal Diseases Retinal Ganglion Cells Retinal Photoreceptors Role Source Stimulus Strychnine Surveys Synapses Testing Tracer Transgenic Organisms Visual system structure aged base cell type connexin 36 flupirtine genetic manipulation insight mature animal mouse model novel patch clamp photoreceptor degeneration presynaptic response retinal neuron retinogeniculate starburst amacrine cell

项目摘要

The long-term goal of this application is to elucidate the mechanisms and functions of inner retina oscillation in development and maintenance of the visual system. The proposal is based on the existence of two independent oscillation mechanisms in adult retina. We hypothesize that these oscillation mechanisms are built-in function of the retina, masked by glutamate released by photoreceptor in normal situation but emergent under deafferentation conditions such as photoreceptor degeneration and complete congenital stationary night blindness to ensure stable connection between the eye and the brain. We have found that deleting connexin 36 (Cx36) but not Cx45 genes can silence retinal oscillation. We have also preliminarily tested mice with photoreceptor degeneration but without Cx36 expression and found that retinogeniculate projections become abnormal. Since retinal oscillation appears to have a biological function, it is important to know mechanistic details of the two mechanisms. Aim-1 will thus focus on delineating the cellular origin of the less understood flupirtine-insensitive mechanism. Aim-2 will stringently test the role of oscillation in maintaining retinofugal projections by genetically manipulating Cx36 gene including inducible inactivation in adult animals after photoreceptor degeneration. In order to understand whether retinal oscillation has other functions, it is necessary to know which retinal neurons oscillate and through what mechanisms. Aim-3 will thus survey synaptic inputs onto genetically identifiable RGCs in two retinal deafferentation mouse models and test the hypotheses that mouse RGCs are more diverse than currently appreciated and that group-specific circuit connection characteristics exist to drive RGCs' unique physiological light responses in different groups. A fruitful outcome will in the short-term generate a resource that contains many genetically identifiable RGC types in mouse and in the long-term assign group-specific morphometric features, intrinsic membrane properties, and light response characteristics to them. These efforts fill knowledge gaps, confer a biological function to retinal oscillation in maintaining RGC central projection, and provide a strong foundation for future inquiries into retinal disease mechanisms and treatment window and/or options.

该应用程序的长期目标是阐明内视网膜的机制和功能