Parallel Pulvinar Pathways

平行的枕小路

• 批准号: 10621175
• 负责人: MARTHA E BICKFORD
• 金额: $ 49.21万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621175
• 关键词: Address; Anatomy; Animal Model; Bilateral; Cell Nucleus; Cells; Code; Contralateral; Coupled; Depressed mood; Diffuse; Disease; Dissection; Dorsal; Dyslexia; Environment; Frequencies; Goals; Head; In Vitro; Injections; Ipsilateral; Knowledge; Label; Laboratories; Lateral Geniculate Body; Light; Link; Location; Methods; Motion; Motion Perception; Motivation; Motor; Movement; Mus; Neurons; Opsin; Pathway interactions; Pattern; Property; Pulvinar structure; Retina; Retinal Ganglion Cells; Rewards; Running; Schizophrenia; Sensory; Signal Transduction; Stream; Structure/Function Nuclei; Synapses; Techniques; Testing; Time; Viral; Viral Vector; Visual; Visual Motion; Visual Pathways; Visual Perception; Visual System; Visual attention; Whole-Cell Recordings; Work; area striata; autism spectrum disorder; behavioral response; brain circuitry; cell cortex; cell type; experimental study; extracellular; in vivo; innovation; insight; nerve supply; neural circuit; novel; optogenetics; parallel processing; receptive field; response; segregation; success; superior colliculus Corpora quadrigemina; theories; visual stimulus

PROJECT SUMMARY / ABSTRACT The concept of parallel pathways that code different aspects of the visual scene has led to many key insights regarding the functional organization of the visual system. Inspired by this concept, the proposed studies focus on parallel visual pathways from the retina to the superior colliculus (SC) through the pulvinar nucleus (PUL). Projections from the SC to the PUL originate from motion-detecting widefield vertical (WFV) cells, and their synaptic organization defines two distinct PUL subdivisions: one that receives ipsilateral topographic WFV projections (“specific”), and one that is innervated by bilateral convergent WFV projections (“diffuse”). These two WFV innervation patterns are correlated with distinct cortical and subcortical connections, as well a variety of histochemical criteria, suggesting that the tectorecipient PUL may be organized into separate visual movement processing streams. However, we currently lack a functional framework that allows us to test this hypothesis and decipher the modular organization of the PUL. We plan to address this gap in knowledge by defining PUL cell types and synaptic inputs in the context of their functional properties. Our guiding hypothesis is that the PUL is composed of two distinct modules that coordinate visual perception with body movements or motivational state to initiate appropriate motor commands. To begin to test this theory, with mice as our animal model, we will use anatomical intersectional viral vector approaches and in vitro whole cell recordings coupled with dual optogenetic activation of cortical and WFV synaptic inputs to define circuit mechanisms that can alter firing properties within each PUL module (Aim 1). We will use in vivo extracellular recordings coupled with optogenetic activation and silencing of synaptic inputs to determine how circuit interactions within each PUL module adjusts receptive field properties (Aim 2). A key innovation of our experiments is the ability to identify PUL neuron subtypes by their unique frequency-dependent responses to optogenetic activation of WFV inputs (“neuron identification via single input dynamics”). This new method will allow us to link detailed in vitro circuit dissection techniques with in vivo recording of visual response properties, providing a framework of PUL function that has thus far been elusive. By comparing two parallel PUL modules, our goal is to understand how visual motion signals are parsed to initiate appropriate behavioral responses.

项目摘要/摘要 对视觉场景的不同方面进行编码的并行路径的概念导致了许多关键的见解 关于视觉系统的功能组织。在这一概念的启发下，拟议的研究重点 从视网膜到上丘(SC)通过枕核(PUL)的平行视觉通路。 从SC到PUL的投射起源于运动检测广域垂直(WFV)细胞，其 突触组织定义了两个不同的PUL细分：一个接受同侧的地形图WFV 投射(“特定”)，以及由双边会聚的WFV投射(“弥漫”)支配的投射。这两个 WFV神经支配模式与不同的皮质和皮质下连接以及各种 组织化学标准，提示TECO受体PUL可能被组织成单独的视觉运动 正在处理数据流。然而，我们目前缺乏一个允许我们测试这一假设的功能框架，并且 破译PUL的模块化组织。我们计划通过定义PUL细胞来解决这一知识缺口 类型和突触输入在其功能属性的上下文中。我们的指导性假设是PUL是 由两个不同的模块组成的，它们将视觉感知与身体运动或动机状态相协调 以启动适当的运动指令。为了开始测试这一理论，以小鼠为动物模型，我们将使用 解剖交叉病毒载体方法和体外全细胞记录与双光遗传相结合 激活皮质和WFV突触输入，以定义可以改变脑内放电特性的电路机制 每个PUL模块(目标1)。我们将使用活体细胞外记录结合光遗传激活和 抑制突触输入以确定每个脉冲模块内的电路交互如何调节感受野 属性(目标2)。我们实验的一个关键创新是能够根据PUL神经元的亚型来识别它们 对WFV输入的光遗传激活的独特的频率依赖反应(通过单个神经元识别 输入动态“)。这一新方法将允许我们将详细的体外电路分离技术与体内联系起来 记录视觉响应属性，提供迄今难以捉摸的PUL功能的框架。 通过比较两个并行的PUL模块，我们的目标是了解视觉运动信号是如何被解析到 启动适当的行为反应。