Can Cortical Plasticity be Directed and Amplified Following Early Loss of Vision?

早期视力丧失后皮质可塑性可以被引导和增强吗？

• 批准号: 8421193
• 负责人: LEAH ANN KRUBITZER
• 金额: $ 37.59万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8421193
• 关键词: Age; Animal Model; Animals; Area; Auditory system; Axon; Behavior; Behavioral; Bilateral; Birth; Blindness; Brain; Cell Density; Child; Development; Didelphidae; Enhancers; Enhancing Lesion; Environment; Exhibits; Eye; Fetus; Financial compensation; Frequencies; Human; Individual; Infant; Injury; Intervention; Invaded; Investigation; Knowledge; Lesion; Mammals; Mediating; Modality; Monodelphis; Monodelphis Domestica; Neocortex; Nervous system structure; Neurons; Newborn Infant; Perinatal; Play; Property; Recovery; Research; Retina; Retinal; Retinal Ganglion Cells; Role; Sensory; Staging; Structure; System; Tactile; Techniques; Testing; Texture; Thalamic structure; Therapeutic; Therapeutic Intervention; Time; Translating; Visual; Visual Acuity; Visual Cortex; Visual impairment; Visual system structure; behavior test; blind; brain shape; density; diencephalon; driving behavior; extrastriate visual cortex; in utero; multisensory; novel; premature; prenatal; public health relevance; relating to nervous system; response; sensory discrimination; somatosensory; subventricular zone; therapy design; visual process; visual processing

DESCRIPTION (provided by applicant): A distinguishing feature of the mammalian neocortex is its remarkable ability to change over a lifetime, especially during early development. Thus, the functional organization and connectivity of each individual's brain is tailored to the physical parameters of a specific environment, permitting behavior to be uniquely optimized for a given sensory milieu. Such plasticity plays an integral role in shaping the brains of normal humans as well those who suffer from severe visual impairments due to retinal abnormalities or cortical lesions that occur at various stages of development. This proposal will investigate the extent of cortical plasticity following experimentally induced manipulations to the visual system during development. Our first objective is to examine the alterations in sensory mediated behavior, as well as changes in the functional organization, connectivity and cellular composition of the neocortex that result from one of two induced neural insults: 1) loss of neocortex that would normally develop into visual cortex; 2) loss of visual input normally provided by the retina. The second objective is to determine if early, pervasive sensory enhancement can be used to direct the functional reorganization of the neocortex and optimize sensory mediated behavior. Manipulations will be made at one of three developmental milestones: 1) Before retinal ganglion cell axons enter the diencephalon and before thalamocortical afferents have reached the cortex. 2) Before eye opening, after thalamocortical afferents have innervated the neocortex, but before axonal pruning and the completion of cortical development. 3) Just after the eyes have opened, when retinofugal and thalamocortical development is established and the subventricular zone and all six cortical layers are present. These animals will be exposed to either a normal or to a tactilely (for bilateral enucleates) or visually (for cortical lesions) enhanced environment. Our animal model, the short-tailed opossum (Monodelphis domestica) is born prematurely, allowing ex-utero manipulations to the nervous system at developmental time points that would be in-utero in other mammals. After the animals have reached maturity we will use behavioral testing combined with electrophysiological and neuroanatomical techniques to examine sensory discrimination, the functional organization and neural response properties of re-organized cortex, cortical and thalamic connectivity, and the cellular composition including neuronal number and density of re-organized cortex. These studies, which are novel in their scope, provide an opportunity to translate detailed knowledge gained at the cellular and systems level to produce significant therapeutic interventions designed to direct multisensory plasticity, and optimize sensory mediated behavior following loss of vision.

描述（由申请人提供）：哺乳动物新皮层的显着特征是其一生中的显着变化能力，尤其是在早期开发期间。因此， 每个人的大脑的功能组织和连通性是根据特定环境的物理参数量身定制的，可以为给定的感觉环境唯一优化行为。这种可塑性在塑造正常人的大脑以及由于视网膜异常或在发育的各个阶段出现的皮质病变而遭受严重视力障碍的人都起着不可或缺的作用。该建议将研究在开发过程中对视觉系统进行实验诱导的视觉系统操纵后皮质可塑性的程度。我们的第一个目标是检查感觉介导的行为的改变，以及由两种诱导神经损伤之一导致的新皮层的功能组织，连通性和细胞组成的变化：1）通常会发展为视觉皮质的新皮层的丧失； 2）视网膜通常提供的视觉输入丢失。第二个目标是确定是否可以使用早期的普遍感觉增强来指导新皮层的功能重组并优化感觉介导的行为。操作将在三个发展里程碑之一中进行：1）在视网膜神经节细胞轴突进入双脑中，然后在丘脑皮层传入到达皮层之前。 2）在开眼界之前，丘脑皮层传入后，新皮层支配了新皮层，但在轴突修剪和皮层发育的完成之前。 3）在睁开眼睛后，建立视网膜和丘脑皮层发育并存在下室内和所有六层皮层层时。这些动物将暴露于正常的或触发的（对于双侧摘除）或视觉（对于皮质病变）上的增强环境。我们的动物模型，短尾的负鼠（单卵石）是过早诞生的，可以在其他哺乳动物的发育时间点之前对神经系统进行前的操纵。动物成熟后，我们将使用与电生理学和神经解剖学技术结合的行为测试来检查感觉区分，重新组织的皮质和丘脑连接性的功能组织和神经反应特性，以及细胞组成，以及包括神经元数和重复的cortex的神经元数和密度。这些研究在其范围中是新颖的研究，提供了一个机会，可以翻译在细胞和系统水平上获得的详细知识，以产生旨在指导多感觉可塑性的重要治疗干预措施，并优化视力丧失后感觉介导的行为。