Adult visual cortical plasticity

描述（申请人提供）：成人视觉皮层的可塑性在知觉学习的正常过程以及中枢神经系统病变后的功能恢复中起着重要作用。我们特别提出，在视觉皮层中看到的正常整合过程被用于中枢神经系统病变后的适应性变化。为了了解成人皮质可塑性的机制及其感知后果，我们将使用一个涉及双目视网膜病变后皮质地形重组的实验模型。我们建立了一个计算模型，将视觉皮质神经元的正常特性与视网膜病变后发生的变化联系起来，并进一步将这些变化与感知填充联系起来。在目前的研究中，我们建议测试该模型的预测，并量化视网膜病变后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，使我们能够在多个时间点和大面积的皮层上跟踪重组过程。这些实验也旨在解决有关损伤模型中皮层地形重映射的普遍性、程度和性质的争议。为了解决机制问题，我们将探讨皮层回路的不同组成部分在重组中的参与。这将通过对细胞、树突和轴突进行体内双光子成像来完成，这些细胞、树突和轴突被携带编码不同荧光团基因的基因工程AAV病毒的神经元感染所标记。我们将研究远程水平连接、来自高阶皮层区域的反馈连接、V1内的层间连接以及树突形态变化的相对贡献。通过这些实验，我们希望了解视网膜变性（如黄斑变性和其他形式的中枢神经系统损伤）后恢复的主要机制。我们的方法还旨在进一步了解视网膜损伤引起的皮质变化的感知后果。除了在研究损伤依赖的可塑性方面的价值外，这些研究将与理解视觉通路中正常经验依赖变化的机制相关，例如与知觉学习相关的变化。本实验将有助于揭示中枢神经系统病变和退行性疾病（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有关，因为可能涉及相同的回路。

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.