Experience-Dependent Plasticity in Superior Colliculus and Natural Visual Behavior

项目总结/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追踪。这些视觉空间定向行为的可塑性 在神经发育障碍如自闭症和神经系统疾病中， 由创伤性经历引起的疾病，如PTSD。因此，发育和可塑性 这些视觉定向行为严重影响健康的视觉加工。为了 最终开发出有针对性的治疗方法，缓解特定的视觉处理缺陷， 与每一种疾病相关，有必要首先了解其背后的机制， 视觉刺激检测和追踪行为的发展和可塑性 从根本上说我们将开始通过调查发展情况来解决这一关键差距， 感觉经验依赖性上级丘特定细胞功能可塑性 因为它们与视觉刺激检测和追求行为的特定变化有关。 上级丘是处理显著环境信息的关键皮层下视觉系统 刺激，从皮层接收大量的输入，并在所有人中介导快速的空间定向行为 哺乳动物该结构中的细胞功能对视觉体验和变化敏感 明显超过发展，和，两类细胞在上级丘被称为 宽场和窄场垂直神经元特别地构成视觉刺激检测和追踪的基础。 然而，我们不知道这些精确的神经回路是如何直接受到视觉影响的。 一生的经验。小鼠提供了一个广泛的遗传途径， 这些工具可以用来缩小我们理解上的差距。在AIM 1中，我们将量化刺激 从出生后第21天到成年的关键发育阶段的检测和追踪行为 来了解这些视觉定向行为在老鼠身上是如何变化的。在AIM 2中，我们将 通过量化来确定特定回路变化是否支持行为的发育变化， 视觉刺激的神经编码，特别是在宽场和窄场细胞电路的 行为动物的上级丘。我们会用高强度的- 密度在体电生理学，光遗传学，病毒介导的电路跟踪，钙成像 和功能性超声成像。在AIM 3中，我们将研究经验依赖性 行为和特定回路功能在上级丘的发展， 通过让老鼠捕捉活的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的神经回路机制的理解。 空间定向行为对视觉感知至关重要。

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.