Adult visual cortical plasticity

成人视觉皮层可塑性

• 批准号: 8013802
• 负责人: CHARLES D GILBERT
• 金额: $ 40.15万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8013802
• 关键词: Acute; Address; Adult; Anesthesia procedures; Animals; Area; Autopsy; Axon; Back; Computer Simulation; Degenerative Disorder; Dendrites; Dependovirus; Engineering; Experimental Designs; Experimental Models; Feedback; Genes; Global Change; Green Fluorescent Proteins; Image; Infection; Label; Learning; Lesion; Life; Macular degeneration; Maps; Measures; Mediating; Microscopy; Modeling; Monitor; Monkeys; Morphology; Nature; Neuraxis; Neurodegenerative Disorders; Neurons; Perceptual learning; Photons; Play; Positioning Attribute; Preparation; Prevalence; Principal Investigator; Process; Property; Recovery; Recovery of Function; Recruitment Activity; Relative (related person); Research; Retina; Retinal; Retinal Degeneration; Role; Scotoma; Series; Signal Transduction; Site; Suggestion; Testing; Time; V1 neuron; Virus; Visual Cortex; Visual Pathways; Work; area striata; awake; cellular imaging; critical period; design; developmental plasticity; experience; fluorophore; improved; in vivo; postnatal; programs; receptive field; research study; response; retinal damage

DESCRIPTION (provided by applicant): Plasticity of the adult visual cortex plays an important role in normal processes of perceptual learning as well as in functional recovery following central nervous system lesions. We propose in particular that the normal integrative processes seen in visual cortex are recruited for adaptive changes following CNS lesions. To understand the mechanisms underlying adult cortical plasticity, as well as its perceptual consequences, we will work with an experimental model involving the reorganization of cortical topography following binocular retinal lesions. We have made a computational model that relates the normal properties of visual cortical neurons to the changes occurring after retinal lesions, and further relates these changes to perceptual fill-in. In the current study we propose to test the predictions of this model, and to quantify the nature of the functional changes in V1 that ensue following retinal lesions. Monitoring the functional reorganization will be done by electrophysiological recordings in awake behaving monkeys, allowing us to follow the process of reorganization over multiple time points and over large areas of cortex. These experiments are also intended to resolve controversies concerning the prevalence, extent and nature of the remapping of cortical topography in the lesion model. To address issues of mechanism, we will explore the involvement of different components of cortical circuitry in the reorganization. This will be done by in vivo 2-photon imaging of cells, dendrites and axons labeled by neuronal infection with genetically engineered AAV virus carrying genes encoding different fluorophores. We will investigate the relative contribution of long-range horizontal connections, feedback connections from higher order cortical areas, and interlaminar connections within V1, as well as changes in dendritic morphology. With these experiments we hope to learn about the central mechanisms of recovery following retinal degenerations, such as macular degeneration and other forms of CNS damage. Our approach is also designed to further our understanding of the perceptual consequences of the cortical changes induced by retinal damage. Beyond their value in the study of lesion dependent plasticity, these studies will be of relevance to understanding the mechanism of normal experience dependent changes in the visual pathway, such as those associated with perceptual learning. The proposed experiments will help reveal the mechanisms of functional recovery following lesions and degenerative diseases of the CNS, including adult macular degeneration. The studies will also be relevant to understanding the normal experience dependent changes associated with perceptual learning, since the same circuits are likely to be involved.

描述(申请人提供)：成人视皮层的可塑性在正常的知觉学习过程中以及中枢神经系统损伤后的功能恢复中发挥着重要作用。我们特别提出，视皮层中正常的整合突起被招募用于中枢神经系统损伤后的适应性变化。为了了解成人皮质可塑性的机制及其知觉后果，我们将使用一个实验模型，该模型涉及双眼视网膜损伤后皮质地形图的重组。我们已经建立了一个计算模型，将视觉皮质神经元的正常属性与视网膜损伤后发生的变化联系起来，并进一步将这些变化与知觉填充联系起来。在目前的研究中，我们建议测试这一模型的预测，并量化视网膜损伤后V1功能变化的性质。监测功能重组将通过对清醒行为的猴子进行电生理记录来完成，使我们能够跟踪多个时间点和大片皮质区域的重组过程。这些实验还旨在解决关于病变模型中皮质地形图重新映射的流行率、范围和性质的争议。为了解决机制问题，我们将探索皮质回路的不同组成部分在重组中的参与。这将通过体内双光子成像来完成，细胞、树突和轴突被神经元感染标记，基因工程AAV病毒携带编码不同荧光团的基因。我们将研究远程水平连接、来自高阶皮质区域的反馈连接和V1内的层间连接的相对贡献，以及树突形态的变化。通过这些实验，我们希望了解视网膜变性后恢复的中心机制，如黄斑变性和其他形式的中枢神经系统损伤。我们的方法还旨在加深我们对视网膜损伤引起的皮质变化的知觉后果的理解。除了它们在研究病变依赖可塑性方面的价值外，这些研究还将有助于理解视觉通路中正常经验依赖性变化的机制，例如与知觉学习相关的机制。拟议的实验将有助于揭示中枢神经系统损伤和退行性疾病(包括成人黄斑变性)后功能恢复的机制。这些研究也将与理解与知觉学习相关的正常经验依赖变化相关，因为可能涉及相同的回路。