The Influence of the Pretectum on the Visual Thalamus

前顶盖对视觉丘脑的影响

• 批准号: 10748541
• 负责人: MARTHA E BICKFORD
• 金额: $ 55.68万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748541
• 关键词: Address; Affect; Amblyopia; Animals; Area; Behavior; Behavioral; Brain; Butyric Acids; Calcium Signaling; Cell Nucleus; Cells; Classification; Complex; Darkness; Depth Perception; Diagnosis; Disease; Disinhibition; Dorsal; Dyslexia; Electron Microscopy; Eye Movements; Felis catus; Fluorescence; Genetic; Glutamates; Image; In Vitro; Injections; Interneurons; Knowledge; Label; Lasers; Lateral Dorsal Nucleus; Lateral Geniculate Body; Light; Link; Mammals; Mediating; Medical; Methods; Miosis disorder; Modeling; Morphology; Motion; Motion Perception; Motor; Movement; Mus; Neurons; Neurotransmitters; Ocular Motility Disorders; Parvalbumins; Pathologic Nystagmus; Pathway interactions; Pattern; Perception; Play; Population; Property; Pulvinar structure; Research; Research Personnel; Retina; Retinal Ganglion Cells; Role; Running; Saccades; Schizophrenia; Sensory; Shapes; Signal Transduction; Source; Speed; Strabismus; Synapses; Techniques; Testing; Thalamic structure; Transgenic Organisms; Viral; Viral Vector; Vision; Visual; Visual Motion; Whole-Cell Recordings; active vision; area striata; awake; calcium indicator; cell type; extracellular; ganglion cell; gaze; in vivo; insight; monocular; novel; optogenetics; rabies viral tracing; receptive field; response; retinogeniculate; tool; transmission process; two-photon; visual stimulus; visual tracking

PROJECT SUMMARY / ABSTRACT The pretectum (PT) is a relatively unexplored brain area in mammals, and it is currently unknown how the PT affects the visual properties of thalamic neurons that underly the complex integration of vision and movement. Here, a team of investigators propose a multifaceted approach - from synapse to behavior – to answer fundamental questions regarding PT circuits (Aim 1), the visual and/or motor response properties of identified PT neurons (Aim 2), the effects of PT input on the response properties of thalamic neurons (Aim 3), and the effects of the PT on visual behavior (Aim 4). Each aim will utilize a combination of novel intersectional circuit labeling techniques, neuronal activation, and recording strategies to probe two identified PT pathways: a GABAergic pathway to the lateral geniculate nucleus (LGN) and the visual sector of the thalamic reticular nucleus (vTRN), and a nonGABAergic pathway to the pulvinar nucleus (PUL) from PT neurons that contain parvalbumin. Aim 1 will use cre-dependent monosynaptic rabies tracing to induce the expression of the calcium indicator GCaMP to classify, using 2P imaging, the receptive field properties and morphology of retinal ganglion cells that innervate PT-LGN/TRN and PT-PUL neurons. Monosynaptic rabies tracing will also be used to characterize cortical and subcortical brain inputs to PT-LGN/TRN and PT-PUL cells; identified PT inputs will subsequently be studied using electron microscopy and in vitro whole cell recordings paired with optogenetic activation to characterize their ultrastructure and synaptic properties. Aim 2 will use in vivo extracellular recordings in awake animals paired with “opto-tagging” to determine the response properties of PT-LGN/TRN and PT-PUL neurons. Aim 3 will use in vivo extracellular recordings from awake animals paired with optogenetic activation of PT inputs to determine the effects of the PT inputs on LGN, vTRN and PUL response properties. Finally, Aim 4 will use cre- and flp-dependent chemogenetic activation of PT-LGN/TRN or PT-PUL neurons to determine if these cells affect stereopsis and/or optokinetic responses. Collectively, these 4 lines of inquiry will provide key information regarding the role of the PT in active vision.

项目概要/摘要 前顶盖（PT）是哺乳动物中相对未被探索的大脑区域，目前尚不清楚 PT 如何影响复杂整合背后的丘脑神经元的视觉特性 在这里，一组研究人员提出了一种多方面的方法 - 从 突触到行为 – 回答有关 PT 回路的基本问题（目标 1）、视觉 和/或已识别的 PT 神经元的运动反应特性（目标 2），PT 输入对 丘脑神经元的反应特性（目标 3），以及 PT 对视觉行为的影响 （目标 4）。每个目标都将利用新颖的交叉电路标记技术的组合， 神经激活和记录策略来探测两个已识别的 PT 途径：GABAergic 通往外侧膝状核（LGN）和丘脑网状视区的通路 核 (vTRN)，以及从 PT 神经元到枕核 (PUL) 的非 GABA 能通路 目标 1 将使用依赖于 cre 的单突触狂犬病追踪来诱导。 钙指示剂 GCaMP 的表达，使用 2P 成像对感受野进行分类 支配 PT-LGN/TRN 和 PT-PUL 的视网膜神经节细胞的特性和形态 单突触狂犬病追踪也将用于表征皮质和皮质下。 随后将研究 PT-LGN/TRN 和 PT-PUL 细胞的大脑输入； 使用电子显微镜和体外全细胞记录结合光遗传学激活 目标2将使用体内细胞外 清醒动物的录音与“光标记”相结合，以确定动物的反应特性 PT-LGN/TRN 和 PT-PUL 神经元将使用清醒时的体内细胞外记录。 与 PT 输入的光遗传学激活配对的动物以确定 PT 输入的影响 最后，Aim 4 将使用依赖于 cre 和 flp 的响应属性。 PT-LGN/TRN 或 PT-PUL 神经元的化学遗传学激活，以确定这些细胞是否影响 总的来说，这 4 条探究路线将提供关键的立体视觉和/或视动反应。 有关 PT 在主动视力中的作用的信息。