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Molecular and functional mechanisms underlying binocular vision

双眼视觉的分子和功能机制

基本信息

批准号：
7782389
负责人：
MRIGANKA SUR
金额：
$ 61.21万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-18 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7782389
关键词：
Acute Address Affect Amblyopia Autistic Disorder Axon Behavior Behavioral Binocular Vision Blindness Calcium Cells Cognition Disorders Contralateral Data Development Dorsal Eph Family Receptors Exhibits Eye FOS gene Functional disorder Generations Genes Image Immunohistochemistry Integral Membrane Protein Ipsilateral Knock-out Knockout Mice Lateral Geniculate Body Lead Link Location Maps Mediating Molecular Mus Nature Neurons Ocular Dominance Ocular dominance columns Pattern Phenotype Physiological Positioning Attribute Process Relative (related person)Retina Retinal Role Sensory Process Shapes Signal Pathway Signal Transduction Social Development Specific qualifier value Strabismus Structure Techniques Testing Tracer Vision Vision Disorders Vision Disparity Visual Visual Cortex Visual Pathways Work area striata axon guidance base design emx2 protein experience in vivo monocular mutant novel optical imaging public health relevance receptive field research study response superior colliculus Corpora quadrigemina therapy design two-photon vision development visual process visual processing

项目摘要

DESCRIPTION (provided by applicant): The exquisite alignment of projections from the two eyes in central visual structures is fundamental for a precise representation of the visual world. We have discovered that the transmembrane protein Ten_m3 is a critical regulator of this process. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral projections relative to contralateral projections, and marked deficits in visual behavior which are reversed by acute monocular inactivation. This indicates that altered interocular interactions act to suppress vision, and that the upstream cortical circuitry is sufficiently intact to mediate visual behavior in the absence of these interactions. These mice allow the opportunity to not only understand the functional consequences of a binocular mismatch, but to probe the mechanisms which underlie binocular vision itself. We will determine the mechanism by which Ten_m3 regulates axon guidance. The pronounced ipsilateral mistargeting predicts that inputs to V1 will be altered in Ten_m3 null mice. We will use anatomical and functional techniques to determine the distribution of ipsilateral and contralateral inputs to V1. We will test the intriguing prediction that functional ocular dominance columns will form in V1, and assess the role of visual experience in their generation. The data suggest there will be a functional misalignment between the ipsilateral and contralateral inputs to V1. The responses, receptive fields and maps of ipsilateral and contralateral inputs, and their interactions, will be examined using electrophysiological recording, intrinsic signal imaging, and two-photon imaging. We will explore the possibility that altered interocular interactions lead to an exaggerated form of interocular suppression and that V1 is an important locus of this effect. Based on its expression pattern, we propose that Ten_m3 regulates cortical arealization and connectivity and will determine its role in these processes. The intracellular signaling pathways which operate downstream of Ten_m3 are unknown. Our data shows that mice lacking zic4 display the inverse phenotype to Ten_m3 mutants. The nature of the interactions between Ten_m3 and zic4 will be determined and novel components of this signaling pathway identified. These findings will have important implications for understanding how abnormal binocular disparity leads to dysfunction in visual disorders such as strabismus and amblyopia, and for developing strategies for their treatment. PUBLIC HEALTH RELEVANCE: Ten_m3 has been shown to be instrumental in development of the visual system. Improper processing of visual inputs can result in amblyopia, strabismus, or blindness; in addition, deficits in sensory processing have been linked to autism and other disorders of cognitive and social development. The planned experiments promise to elucidate the mechanisms by which Ten_m3 expression affects the development of binocular vision, and thus to provide a novel basis for the design of therapies for visual dysfunction.

描述（由申请人提供）：中央视觉结构中两只眼睛的投影的精确对齐是精确表示视觉世界的基础。我们发现跨膜蛋白 Ten_m3 是该过程的关键调节因子。缺乏 Ten_m3 的小鼠在同侧投影相对于对侧投影的映射方面表现出严重异常，并且视觉行为存在明显缺陷，这种缺陷可以通过急性单眼失活来逆转。这表明改变的眼间相互作用会抑制视力，并且上游皮质回路足够完整，可以在没有这些相互作用的情况下介导视觉行为。这些小鼠不仅让我们有机会了解双眼失配的功能后果，还可以探索双眼视觉本身的机制。我们将确定 Ten_m3 调节轴突引导的机制。明显的同侧误定位预测 Ten_m3 无效小鼠中 V1 的输入将发生改变。我们将使用解剖学和功能技术来确定 V1 的同侧和对侧输入的分布。我们将测试功能性眼优势列将在 V1 中形成的有趣预测，并评估视觉体验在其生成中的作用。数据表明 V1 的同侧和对侧输入之间存在功能错位。将使用电生理记录、固有信号成像和双光子成像来检查同侧和对侧输入的响应、感受野和图及其相互作用。我们将探讨改变眼间相互作用导致过度形式的眼间抑制的可能性，并且 V1 是这种效应的重要部位。基于其表达模式，我们提出 Ten_m3 调节皮质区域化和连接性，并将决定其在这些过程中的作用。 Ten_m3 下游的细胞内信号传导途径尚不清楚。我们的数据显示，缺乏 zic4 的小鼠表现出与 Ten_m3 突变体相反的表型。 Ten_m3 和 zic4 之间相互作用的性质将被确定，并确定该信号通路的新成分。这些发现对于理解异常双眼视差如何导致斜视和弱视等视觉障碍的功能障碍以及制定治疗策略具有重要意义。公共健康相关性：Ten_m3 已被证明有助于视觉系统的发育。视觉输入处理不当可能导致弱视、斜视或失明；此外，感觉处理缺陷与自闭症和其他认知和社会发展障碍有关。计划中的实验有望阐明 Ten_m3 表达影响双眼视觉发育的机制，从而为视觉功能障碍疗法的设计提供新的基础。