Development of direction selectivity maps

方向选择性图的开发

• 批准号: 10219270
• 负责人: Alexandre Tiriac
• 金额: $ 11.14万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219270
• 关键词: Action Potentials; Adult; Age; Animals; Behavior; Calcium; Cells; Controlled Environment; Cues; Data; Detection; Development; Dorsal; Ephrin B Receptor; Ephrins; Exhibits; Eye; Fire - disasters; Gravitation; Head; Image; Instruction; Knock-out; Knockout Mice; Life; Location; Maps; Modeling; Molecular; Motion; Motion Perception; Mus; Operative Surgical Procedures; Organism; Pharmacogenetics; Play; Population; Process; Publishing; Retina; Retinal Ganglion Cells; Role; Seminal; Sensory; Specificity; Surface; Testing; Transgenic Mice; Vision; Visual; Visual Cortex; Work; axon guidance; dark rearing; environmental enrichment for laboratory animals; experience; experimental study; falls; ganglion cell; neural circuit; novel; novel therapeutics; optic flow; orbit muscle; postnatal; preference; response; statistics; tool; two-photon; visual deprivation; visual stimulus

PROJECT SUMMARY How does our ability to detect motion develop and to what extent does sensory experience contribute? In mice, the detection of motion begins in the retina. There, direction selective ganglion cells (DSGCs) fire more action potentials in response to visual stimuli moving in one direction, called the preferred direction, than visual stimuli moving in the opposite direction, called the null direction. In the adult retina, the preferred directions of DSGCs cluster along 4 directions. The relative orientation of these clusters varies across the surface of the retina, creating a direction selectivity map. The factors which underlie the development of the direction selectivity map is unknown. Two recent experiment indicate visual experience is involved. The first is that the preferred direction of DSGCs cluster along the axes defined by optic flow, i.e. the trajectories of apparent motion mapped onto the retinal surface. The second is from the Feller lab showing that the clustering of DSGCs preferred directions along the 4 axes requires visual experience. In Aim1, I present strong preliminary evidence that demonstrates that the map is established at eye-opening and is not altered after visual deprivation, contradicting a role for activity. Although visual experience does not seem necessary for establishing the direction selectivity map, it may play a role in refining it. For example, raising a mouse in an artificial environment that enriches for specific orientations leads to an overrepresentation of cortical cells that prefer that orientation and the process is thought to be instructive rather than permissive. Therefore, in specific aim 2, I will determine whether altered visual experience, specifically enriched for optic flow, refines the direction selectivity map. Finally, in Aim 3, we explore the factors that influence the organization of the direction selectivity map at eye opening. First, we test whether retinal waves, which are spontaneous depolarizations of retinal ganglion cells that occur exclusively during the first two weeks of postnatal life, play a role. These waves are the primary driver of activity before eye opening in the direction selectivity circuit and even exhibit a propagation bias toward forward optic flow. We propose a pharmacogenetic experiments to determine whether disruption of retinal waves alters the organization of the map. Second, we begin to explore the role of transient molecular gradients that are expressed in the retina when the direction selectivity circuit is developing. Specifically, I provide evidence that the EphB receptor of the ephrinB axon guidance molecule exhibits a similar distribution gradient as the dorsal- ventral DSGC preferred directions. We will then look at maps in a mouse lacking EphB receptors in the retina.

项目摘要 我们感知运动的能力是如何发展的？感官体验在多大程度上起作用？在 在老鼠身上，对运动的检测始于视网膜。在那里，方向选择性神经节细胞（DSGCs） 动作电位响应视觉刺激移动在一个方向，称为首选方向，比视觉 在相反方向上移动的刺激，称为零方向。在成人视网膜中， DSGCs在沿着4个方向聚集。这些簇的相对取向在视网膜表面上是不同的， 创建方向选择性图。发展方向选择性地图的基础因素 不明最近的两个实验表明，视觉经验参与其中。第一个是， DSGCs的簇沿着由光流定义的轴，即映射到 视网膜表面第二个来自Feller实验室，显示DSGCs的聚集倾向于沿着方向 4轴需要视觉体验。在目标1中，我提出了强有力的初步证据，表明 图是建立在眼睛睁开，并没有改变后，视觉剥夺，矛盾的作用，为活动。 虽然视觉经验似乎不是建立方向选择性图所必需的，但它可能 例如，在人工环境中饲养一只老鼠， 取向导致倾向于该取向的皮层细胞的过度表达， 要有教育性而不是放任。因此，在具体目标2中，我将确定 经验，特别是丰富的光流，细化方向选择性地图。 最后，在目标3中，我们探讨了影响方向选择性映射组织的因素 睁开眼睛。首先，我们测试是否视网膜波，这是自发去极化的视网膜神经节 只在出生后的头两周内出现的细胞发挥了作用。这些波是 在方向选择性电路中，在眼睛睁开之前的活动驱动器，甚至表现出朝向 前向光流我们提出了一个药物遗传学实验，以确定是否中断视网膜波 改变了地图的结构其次，我们开始探索瞬时分子梯度的作用， 在方向选择性回路发育时在视网膜中表达。具体来说，我提供的证据表明， ephrinB轴突导向分子的EphB受体表现出与背侧- 腹侧DSGC偏好方向。然后，我们将研究视网膜中缺乏EphB受体的小鼠的地图。