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Dynamic modulation of retinal ribbon-type synapses

视网膜带状突触的动态调制

基本信息

批准号：
8632259
负责人：
HENRIQUE Prado VON GERSDORFF
金额：
$ 38.5万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8632259
关键词：
Adult Amacrine Cells American Applications Grants Biological Assay Blindness Buffers Calcium Cells Cone Coupling Cyclic AMP Data Detection Development Devices Docking Egtazic Acid Electric Capacitance Electrophysiology (science)Exocytosis Eye Funding Future Glutamates Glycine Image Impairment In Situ Inhibitory Synapse Interneurons Kinetics Knowledge Lead Life Light Macular degeneration Measurement Measures Membrane Mental Depression Monitor Mus Neurons Neurotransmitters Output Pattern Photoreceptors Physiologic pulse Physiological Plastics Probability Property Prosthesis Recovery Recruitment Activity Recycling Retina Retinal Retinal Diseases Retinitis Pigmentosa Series Slice Stimulus Synapses Synaptic Transmission Synaptic Vesicles Synaptic plasticity Techniques Testing Time Vesicle Vision Vision Disorders Visually Impaired Persons Work controlled release design ganglion cell insight patch clamp postnatal postsynaptic presynaptic public health relevance research study response retinal prosthesis sensor synaptic depression time use voltage clamp

项目摘要

PROJECT SUMMARY Bipolar cell and amacrine cell synapses are key components of the vertebrate retinal circuitry with multiple specialized functions. The underlying cellular mechanisms that control transmitter output from the ribbon-type synapses of bipolar cells and the conventional inhibitory synapses of amacrine cells, under vastly different ambient light conditions, are still poorly understood in the mammalian retina. Here we propose to do a series of patch-clamp electrophysiology and calcium imaging experiments on single amacrine cells of the mouse retina. This allows us to measure both presynaptic Ca2+ currents and evoked changes in membrane capacitance that assay synaptic vesicle exocytosis in real time from a living cell. We will apply calcium imaging and membrane capacitance techniques to the AII amacrine cell, a major interneuron in the mammalian retina that releases glycine at conventional active zones that contain a large cluster of synaptic vesicles. We will determine the overall capacity for exocytosis of a single AII amacrine cell. We will test the hypothesis that AII amacrine cells contain three distinct readily releasable pools of vesicles that have different sizes and kinetics of exocytosis. The mechanisms that maintain and modulate glycine release and short-term plasticity from AII amacrine cells are not known. We will test the hypothesis that cAMP levels modulate the kinetics of glycine release, the size of the readily releasable vesicle pool, and the short-term plasticity at AII amacrine cell synapses. We will also perform these measurements on AII amacrine cells during early postnatal development. We will test the hypothesis that the coupling between vesicles and the Ca2+ sensor for exocytosis becomes tighter during early development as Ca2+ currents increase in size and as Ca2+ channels become more colocalized with docked vesicles at the active zones of AII amacrine cells. Finally, using a combination of voltage-clamp and current- clamp recordings we will measure the degree of exocytosis from single AII amacrine cells that is evoked by physiological stimuli, namely, light stimuli of different intensities. In summary, the results of this grant proposal will provide a better understanding of how AII amacrine cells modulate bipolar cell terminal release via dynamic and plastic inhibitory synapses.

项目总结