Development of direction selectivity in retina

视网膜方向选择性的发展

• 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
• 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

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好，其中几种分子相互作用已被确定为 对于早期建立粗略的视觉地图至关重要，而称为视网膜的早期自发活动 在睁眼之前的波和睁眼之后的视觉剥夺导致地图细化。 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 强烈地响应于在优选方向上移动的图像而微弱地响应于在相反方向上移动的图像， 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时，视网膜上的图像以及用于感知物体内的运动 视觉场景。方向选择性神经节细胞的优选方向沿着沿着四个方向聚集， 沿着沿着两个光流轴对齐，我们将这种组织称为方向选择性图。的机制 指导这个方向选择性地图的发展是未知的。 在这里，我们建议使用最先进的双光子钙成像，电生理学， 转基因小鼠策略，以确定发展方向的机制 选择性图谱特别是，我们将确定是否神经信号，无论是通过缝隙连接或视网膜波， 在这些方向选择性图的形成中起关键作用。最后，我们将测试候选的突触基因 在RNA-seq筛选中鉴定出的分子可能指示功能性抑制性突触的出现， 方向选择性反应的基础