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.

神经回路的发展涉及分子线索与神经活动之间的丰富相互作用。这是也许在视觉系统中研究了最精心的研究，其中几种分子相互作用被确定为对于早期建立粗视觉地图至关重要，而两种早期自发活动称为视网膜眼睛张开和视觉剥夺之前的波浪会导致地图细化。我们在视网膜的方向选择性神经节细胞中研究了这个问题。方向选择性神经节细胞对沿首选方向移动的图像的反应强烈，而对相反的图像却微弱地响应，或无效方向。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时，视网膜上的图像以及感知物体的运动视觉场景。方向选择性神经节细胞沿着四个方向聚集的优选方向沿两个光学流轴对齐，一个组织我们称为方向选择性图。机制该指导该方向选择性图的开发未知。在这里，我们建议使用最先进的两光子钙成像，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，我们将通过间隙连接或视网膜波确定神经信号传导是在这些方向选择性图的形成中起关键作用。最后，我们将测试候选人突触在RNA-seq屏幕上鉴定出的分子，该分子可能指示功能抑制突触的出现这是选择性响应的基础。