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.

项目总结/摘要 编码视觉场景的不同方面的平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。受此概念的启发，建议的研究重点 在从视网膜通过枕核（PUL）到上级丘（SC）的平行视觉通路上。 从SC到PUL的投影源自运动检测宽场垂直（WFV）单元，并且其 突触组织定义了两个不同的PUL亚区：一个接受同侧地形WFV 一种是由双侧会聚WFV投射支配的（“特异性”），另一种是由双侧会聚WFV投射支配的（“弥散性”）。这两 WFV神经支配模式与不同的皮质和皮质下连接以及各种不同的 组织化学标准，表明tectorecepitivePUL可能被组织成单独的视觉运动 处理流。然而，我们目前缺乏一个功能框架，使我们能够测试这一假设， 破译PUL的模块化组织。我们计划通过定义PUL单元来解决这一知识差距 类型和突触输入在其功能属性的上下文中。我们的指导假设是，PUL是 由两个不同的模块组成，协调视觉感知与身体运动或动机状态 以启动适当的电机指令。为了开始验证这一理论，我们将使用小鼠作为我们的动物模型， 解剖学交叉病毒载体方法和体外全细胞记录结合双重光遗传学 激活皮层和WFV突触输入，以定义可以改变内部放电特性的电路机制。 每个PUL模块（目标1）。我们将使用体内细胞外记录结合光遗传学激活， 突触输入的沉默，以确定每个PUL模块内的电路相互作用如何调节感受野 属性（目标2）。我们实验的一个关键创新是能够通过PUL神经元亚型的表达来识别PUL神经元亚型。 对WFV输入的光遗传学激活的独特频率依赖性响应（“经由单个神经元识别”）。 输入动态”）。这种新方法将使我们能够将详细的体外回路解剖技术与体内回路解剖技术联系起来。 记录的视觉反应特性，提供了一个框架的PUL功能，迄今为止一直难以捉摸。 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的， 做出适当的行为反应。