Development and function of the Xenopus tadpole retinotegmental projection

新生的神经元（脑细胞）具有惊人的自我组装成电路的能力-功能连接的神经元组。这些回路产生了我们的感知、思想、情感和行为。了解神经元如何自组装成电路是神经科学领域的一个重要目标，也是本项目的总体目标。这在哺乳动物中很难研究，因为它们有数十亿的神经元，复杂的电路和多变的行为。这个项目研究了一个更易于实验处理的回路：非洲爪蟾（Xenopus）蝌蚪的视觉系统。以往对蝌蚪视觉系统的研究主要集中在视网膜顶盖投射，这是一个由眼睛中的视网膜神经节细胞（RGC）和视顶盖之间的突触组成的回路，视顶盖是两栖动物中脑背侧（顶部）表面上的主要视觉处理中心。在当前项目的准备工作中，我们的特点是第二个投影之间的视网膜神经节细胞从爪蟾的眼睛和腹侧（底部）中脑称为retinotegmental投影。初步数据表明，这两种投射是不同的，在视觉系统中执行不同的功能。本研究的目的是详细描述视网膜被盖投射的发育和功能。总的来说，这项工作将为神经回路如何形成和执行特定功能提供重要的新见解。该项目的教育和更广泛的影响活动包括为非理科本科生教授"视觉与艺术"课程，以及学生设计和进行实验以确定环境因素如何影响非洲爪蟾胚胎发育的高级发育科学实验室课程。神经元如何自我组装成引起行为的电路是神经科学中的一个基本问题。几十年来，非洲爪蟾蝌蚪视网膜顶盖投射-眼睛中视网膜神经节细胞（RGC）和中脑视顶盖之间的突触-一直是研究这个问题的流行模型。但视网膜顶盖投射只是脊椎动物视觉系统的几个组成部分之一。我们最近的工作表明，蝌蚪的颜色依赖性趋光性不需要视顶盖，但需要被盖，中脑的一个区域，位于腹侧视顶盖。我们还发现了几个颜色调谐的神经元群体在被盖。通过额外的解剖学和电生理学研究，我们确定了视网膜被盖投射，从RGCs到中脑被盖神经元的直接投射。这种投射似乎缺乏视网膜顶盖投射所显示的发育可塑性，这表明一个更硬的电路。一个高度保守的视网膜被盖投射，称为辅助视系统（AOS），已被描述在广泛的成年脊椎动物，从青蛙到人类。它与视动反应和视动反应相关-分别是反射性的身体和眼睛运动，当生物体在空间中移动时，它们可以稳定视觉。我们在蝌蚪中研究的视网膜被盖投射很可能至少部分是AOS。通过电生理学为基础的方法和电路跟踪相结合，这项工作将提供一个详细的描述非洲爪蟾蝌蚪retinotegmental投影的发展和分化及其在处理视觉stimulation.This奖项反映了NSF的法定使命的作用，并已被认为是值得通过使用该基金会的智力价值和更广泛的影响审查标准进行评估的支持。

New-born neurons (brain cells) have the amazing ability to self-assemble into circuits – groups of functionally connected neurons. These circuits give rise to our perceptions, thoughts, emotions, and behaviors. Understanding how neurons self-assemble into circuits is an important aim in the field of neuroscience, and it is the overall aim of this project. This would be difficult to study in mammals with their billions of neurons, complex circuits, and variable behaviors. This project studies a more experimentally tractable circuit: the developing visual system of the African Clawed Frog (Xenopus) tadpole. Previous studies on the tadpole visual system have focused on the retinotectal projection, a circuit consisting of the synapse between the retinal ganglion cells (RGCs) in the eye and the optic tectum, a major visual processing center on the dorsal (top) surface of the amphibian midbrain. In preparatory work for the current project, we characterized a second projection between the retinal ganglion cells from the Xenopus eye and the ventral (bottom) midbrain called the retinotegmental projection. Preliminary data indicate that these two projections are built differently and carry out different functions within the visual system. The goal of this project is to provide a detailed description of the development and function of the retinotegmental projection. Overall, this work will contribute important new insights about how neural circuits form and carry out specific functions. Educational and broader impact activities for this project include teaching a “Vision and Art” course for non-science undergraduates, and an upper-level developmental science lab course in which students design and carry out experiments to determine how environmental factors impact the developing Xenopus embryo. How neurons self-assemble into circuits that give rise to behaviors is a fundamental question in neuroscience. For decades, the Xenopus tadpole retinotectal projection – the synapse between the retinal ganglion cells (RGCs) in the eye and the midbrain optic tectum – has served as a popular model to study this question. But the retinotectal projection is only one of several components of the vertebrate visual system. Our recent work shows that color-dependent phototaxis in tadpoles does not require the optic tectum, but does require the tegmentum, a region of the midbrain that lies ventral to the optic tectum. We also found several color-tuned neuronal populations in the tegmentum. Through additional anatomical and electrophysiological studies, we identified a retinotegmental projection, a direct projection from the RGCs to the midbrain tegmental neurons. This projection appears to lack the developmental plasticity displayed by the retinotectal projection, suggesting a more hard-wired circuit. A highly conserved retinotegmental projection, termed the accessory optic system (AOS), has been described across a wide range of adult vertebrates, from frogs to humans. It is associated with optomotor and optokinetic responses – reflexive body and eye movements, respectively, that stabilize vision as the organism moves through space. It is likely that the retinotegmental projection we are studying in the tadpole is, at least in part, the AOS. Through a combination of electrophysiology-based approaches and circuit tracing, this work will provide a detailed description of the development and differentiation of the Xenopus tadpole retinotegmental projection and its role in processing visual stimuli.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.