Development of direction selectivity maps

我们感知运动的能力是如何发展起来的？感官体验在多大程度上起到了作用？在……里面 老鼠，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)激发更多 动作电位对视觉刺激在一个方向移动的反应，称为首选方向，而不是视觉 刺激以相反的方向移动，称为零方向。在成人视网膜中，偏爱的方向 DSGCs沿4个方向聚集。这些簇的相对方向在视网膜表面上各不相同， 创建方向选择性地图。发展方向选择性地图的基础因素 是未知的。最近的两项实验表明，这与视觉体验有关。第一个是首选的方向 沿光流定义的轴线聚集的DSGCs，即映射到 视网膜表面。第二个来自费勒实验室的研究表明，DSGCs的集群沿着 这4个轴需要视觉体验。在Aim1中，我提出了强有力的初步证据，证明 MAP是在睁开眼睛时建立的，在视觉剥夺后不会改变，这与活动的作用相矛盾。 虽然视觉体验似乎不是建立方向选择性地图所必需的，但它可以 在提炼它方面发挥作用。例如，在人工环境中饲养一只老鼠，这种环境丰富了特定的 定向导致了偏爱定向的皮质细胞的过度表达，这一过程被认为是 要有教育意义，而不是放任。因此，在具体的目标2中，我将确定是否改变了视觉 经验，特别是丰富的光流，完善了方向选择性地图。 最后，在目标3中，我们探讨了影响方向选择性地图组织的因素 睁开眼睛的时候。首先，我们测试视网膜波，它是视网膜神经节的自发去极化 仅发生在出生后前两周的细胞起着一定的作用。这些波是主要的 在方向选择电路中眼睛打开之前的活动的驱动，并且甚至表现出传播偏置 前向光流。我们提出了一种药物遗传学实验来确定视网膜波的破坏 更改地图的组织。第二，我们开始探索瞬时分子梯度的作用 在视网膜中表达，当方向选择回路正在发展时。具体地说，我提供的证据是 肾上腺素B轴突导向分子的EphB受体表现出与背侧EphB受体相似的分布梯度。 腹侧DGC首选方向。然后，我们将查看视网膜中缺乏EphB受体的小鼠的地图。

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.