Experience-Dependent Plasticity in Superior Colliculus and Natural Visual Behavior

项目摘要/摘要 我们的长期目标是识别和理解视觉可塑性的潜在机制 刺激检测和视觉引导的追逐。这些视觉空间定向行为的可塑性 既患有自闭症等神经发育障碍，也患有神经性疾病 创伤后应激障碍等创伤性经历引起的精神障碍。因此，发展和可塑性 其中，视觉定向行为对健康的视觉加工有着至关重要的影响。为了 最终开发针对性的治疗方法来缓解特定的视觉处理缺陷 与每一种疾病相关的是，有必要首先了解其潜在的机制 视觉刺激检测和追逐行为的发展和可塑性 从根本上说。我们将开始解决这一关键差距，通过调查发展和 上丘特定细胞类型功能的感觉经验依赖性可塑性 在老鼠身上，因为它们与视觉刺激检测和追逐行为的具体变化有关。 上丘是一个关键的皮质下视觉系统，负责处理突出的环境 刺激，接受来自皮质的大量输入，并在所有人中调节快速空间定向行为 哺乳动物。这个结构中的细胞的功能对视觉体验和变化很敏感 上丘中有两类细胞，称为上丘 广域和窄域垂直神经元是视觉刺激检测和追踪的具体基础。 然而，我们不知道这些精确的神经回路是如何受到视觉的直接影响的 在生活中体验。鼠标提供了一种广泛的复杂基因 可以用来弥合我们理解上的这一差距的工具。在目标1中，我们将量化刺激 出生后第21天至成年期关键发育阶段的检测和追逐行为 以了解这些视觉定向行为在鼠标中是如何变化的。在AIM 2中，我们将 通过量化来确定特定的回路变化是否支持行为的发育变化 视觉刺激的神经编码，特别是在大脑的宽视野和窄视野细胞电路中。 有行为的动物的上丘。我们将测量特定的神经活动使用高- 体内密度电生理学、光遗传学、病毒介导的电路示踪、钙成像 和功能超声成像。在AIM 3中，我们将研究经验依赖 大鼠上丘行为功能和特殊回路功能的发育 通过允许老鼠捕猎活昆虫来操纵视觉体验(丰富)。总体而言，这 这项工作将促进我们对成功背后的神经回路机制的理解 对视觉感知至关重要的空间定向行为。

PROJECT SUMMARY/ABSTRACT Our long term goal is to identify and understand the mechanisms underlying plasticity in visual stimulus detection and visually-guided pursuit. Plasticity in these visuospatial orienting behaviors are perturbed in both neurodevelopmental disorders such as autism as well as neurological disorders resulting from traumatic experiences such as PTSD. Thus, development and plasticity of these visual orienting behaviors critically impact healthy visual processing. In order to ultimately develop targeted therapies that alleviate the specific visual processing deficits associated with each disorder, it is necessary to first understand the mechanisms that underlie the development and plasticity of visual stimulus detection and pursuit behaviors more fundamentally. We will start to address this critical gap by investigating the development and sensory experience-dependent plasticity of function of specific cell types of the superior colliculus in the mouse as they relate to specific changes in visual stimulus detection and pursuit behavior. The superior colliculus is a key subcortical visual system that processes salient environmental stimuli, receives substantial input from cortex and mediates rapid spatial orienting behavior in all mammals. The function of cells in this structure are sensitive to visual experience and change significantly over development, and, two classes of cells in the superior colliculus known as the wide- and narrow-field vertical neurons specifically underlie visual stimulus detection and pursuit. However, we do not understand how these precise neural circuits are directly impacted by visual experience throughout life. The mouse affords access to a broad range of sophisticatedgenetic tools that may be used to close this gap in our understanding. In AIM 1, we will quantify stimulus detection and pursuit behaviors at key developmental stages from postnatal day 21 to adulthood to understand how these visual orienting behaviors change in the mouse. In AIM 2, we will determine whether specific circuit changes support developmental changes in behavior by quantifying the neural encoding of visual stimuli specifically in the wide- and narrow-field cell circuits of the superior colliculus in the behaving animal. We will measure specific neural activity using high- density in vivo electrophysiology, optogenetics, virus mediated circuit tracing, calcium imaging and functional ultrasound imaging. In AIM 3, we will study the experience-dependent development of both behavior and specific circuit function in the superior colliculus by manipulating visual experience by allowing mice to hunt live insects (enrichment). Overall, this work will advance our understanding of the neural circuit mechanisms underlying successful spatial orienting behaviors that are essential for visual perception.