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Synaptic Architecture and Mechanisms of Direction Selectivity in Primate Retina

灵长类视网膜突触结构和方向选择性机制

基本信息

批准号：
10093434
负责人：
DENNIS MICHAEL DACEY
金额：
$ 38.88万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10093434
关键词：
Amacrine Cells Architecture Area Axon Beds Calcium Calcium Signaling Cell physiology Cells Clinical Color Coupling Data Dendrites Detection Development Disease Elements Functional Imaging Human Image Interneurons Light Link Location Macaca Mediating Methods Modeling Monkeys Morphology Motion Motion Perception Movement Mus Neurobiology Ocular Physiology Oryctolagus cuniculus Outcome Output Pathway interactions Physiological Physiology Population Primates Property Radial Research Retina Role Series Stimulus Structure Sum Synapses Testing Time Tracer Trees Vision Vision research Visual Pathways cell type cellular imaging fovea centralis ganglion cell high resolution imaging imaging modality model development neuromechanism nonhuman primate novel postsynaptic presynaptic programs receptive field reconstruction response retinal imaging sight restoration starburst starburst amacrine cell synaptic inhibition tool tool development visual neuroscience visual processing

项目摘要

A major research challenge for neurobiology is to understand the neural mechanisms that give rise to an extreme diversity of parallel visual pathways and ultimately the contributions that these pathways make to our perception of motion, form and color. For motion perception the cell types, circuits and synaptic mechanisms that mediate selectivity to the direction of moving stimuli have been intensively studied in the non-primate mammal for decades and over a dozen distinct direction selective pathways are recognized in the mouse retina together with growing evidence for similarly diverse underlying neural mechanisms. The great complexity of the visual pathways found in the mouse is mirrored in the primate, yet surprisingly the abundant direction selective ganglion cells have not been previously identified. The broad long-term objective of this new research program is to elucidate for the first time the cell types, circuits, synaptic organization and underlying cellular mechanisms for direction selectivity in the macaque monkey retina, as an ideal model for human visual processing centered around the fovea. Our proposed research plan arises from a series of discoveries that opens a door to the first detailed study of both the visual physiology and synaptic organization of direction selective circuitry in the macaque retina. In preliminary studies we have identified the primate ON-OFF direction selective ganglion cell as the recursive bistratified type and have developed new methods that permit systematic targeting of this cell type for analysis. The synaptic physiology and directional tuning of this ganglion cell type are the focus of Aim 1 where we test the hypothesis that directional selectivity in the primate is radially aligned with respect to the fovea. Second, we have developed reliable methods for targeting the starburst amacrine cell type, the key retinal interneuron in the direction selective circuit, for both physiological analysis and connectomic circuit reconstruction for the first time. Preliminary data reveal novel features of starburst receptive field structure, directional tuning and connectivity providing the focus for Aim 2 where we test new hypotheses for the cellular origins of direction selectivity and its synaptic transfer to ganglion cells. Finally, we have discovered direction selectivity in the poly-axonal spiking A1 amacrine cell type and evidence for a functional link to ON-OFF direction selective ganglion cells. The focus of Aim 3 therefore is to test the hypotheses that the A1 cells unique axonal component provides synaptic input to both starburst and ON-OFF direction selective ganglion cells, and determine the role of the A1 cells unique dendro-axonal structure in direction selectivity. In sum the broad aim is to characterize the directional tuning properties of these three cell types, and to use connectomics for the first time to determine the underlying synaptic interactions that create direction selectivity in the primate retina. Outcomes will thus have a specific impact on understanding of mechanisms motion processing in human vision and more broadly on growing applications of the primate model for the development of tools and methods for vision restoration.

神经生物学的一个主要研究挑战是理解产生神经反应的神经机制