Development of direction selectivity in retina

视网膜方向选择性的发展

基本信息

批准号：
10532188
负责人：
Marla Feller
金额：
$ 39.11万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10532188
关键词：
Address Adult Amacrine Cells Anatomy Animals Anterior Automobile Driving Binding Biological Assay Biological Models Calcium Candidate Disease Gene Cells Congenital Abnormality Coupling Cues Data Development Dorsal Electrophysiology (science)Eye Gap Junctions Goals Grant Head Image Inhibitory Synapse Knockout Mice Location Maps Mediating Methods Modeling Molecular Motion Movement Mus Neurologic Optics Pattern Peripheral Physiological Play Population Positioning Attribute Reflex action Retina Retinal Ganglion Cells Role Spatial Distribution Synapses System Testing Transgenic Mice Variant Visual Visual Fields Visual System Work experimental study ganglion cell mouse model neural neural circuit neurodevelopment neurotransmission object motion oculomotor optic flow receptive field response starburst amacrine cell synaptic inhibition synaptogenesis transcriptome sequencing two-photon visual deprivation visual map visual stimulus voltage clamp

项目摘要

The development of neural circuits involves a rich interplay between molecular cues and neural activity. This is perhaps most well studied in the visual system, where several molecular interactions have been identified as being critical for early establishment of coarse visual maps while both early spontaneous activity called retinal waves prior to eye opening and visual deprivation after eye opening leads to map refinement. We study this question in a direction-selective ganglion cells of the retina. Direction selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction. Direction-selective ganglion cells are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene as well as for sensing the movement of objects within the visual scene. The preferred directions of direction selective ganglion cells cluster along four directions that align along two optic flow axes, an organization we refer to as the direction selectivity map. The mechanisms that instruct the development of this direction selectivity map are unknown. Here we propose to use a combination of state-of-the-art two-photon calcium imaging, electrophysiology, and transgenic mouse strategies to determine the mechanisms that underlie the development of the direction selectivity maps. In particular, we will determine if neural signaling, either through gap junctions or retinal waves, play a critical role in the formation of these direction selectivity maps. Finally, we will test candidate synaptogenic molecules identified in an RNA-seq screen that may instruct the emergence of the functional inhibitory synapses that underlie direction selective responses.

神经回路的发育涉及分子线索和神经活动之间丰富的相互作用。这是也许在视觉系统中研究得最多，其中几种分子相互作用已被确定为对于粗略视觉图的早期建立至关重要，而称为视网膜的早期自发活动睁眼前的波浪和睁眼后的视觉剥夺会导致地图细化。我们在视网膜的方向选择性神经节细胞中研究这个问题。方向选择性神经节细胞对沿首选方向移动的图像反应强烈，对沿相反方向移动的图像反应较弱，或零方向。方向选择性神经节细胞对于驱动稳定的眼运动反射至关重要当我们在视觉场景中移动以及感知内部物体的运动时，视网膜上的图像视觉场景。方向选择性神经节细胞的首选方向沿着四个方向聚集：沿着两个光流轴对齐，我们将这种组织称为方向选择性图。机制指导该方向选择性图的开发的因素尚不清楚。在这里，我们建议结合使用最先进的双光子钙成像、电生理学和转基因小鼠策略以确定方向发展的机制选择性图。特别是，我们将确定神经信号传导，无论是通过间隙连接还是视网膜波，在这些方向选择性图的形成中起着至关重要的作用。最后，我们将测试候选突触发生 RNA-seq 筛选中鉴定出的分子可能指导功能性抑制性突触的出现这是方向选择性反应的基础。