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: 8600683
• 负责人: LEAH ANN KRUBITZER
• 金额: $ 36.75万
• 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/8600683
• 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）：哺乳动物新皮质的一个显着特征是其在一生中特别是在早期发育过程中显着的变化能力。因此， 每个人大脑的功能组织和连接都是根据特定环境的物理参数量身定制的，从而允许针对给定的感官环境对行为进行独特的优化。这种可塑性在塑造正常人以及由于不同发育阶段发生的视网膜异常或皮质病变而遭受严重视力障碍的人的大脑方面发挥着不可或缺的作用。该提案将研究发育过程中对视觉系统进行实验诱导操作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，以及新皮质的功能组织、连接性和细胞组成的变化，这些变化是由两种诱发的神经损伤之一引起的：1）通常会发育成视觉的新皮质的丧失皮质； 2）通常由视网膜提供的视觉输入丧失。第二个目标是确定早期普遍的感觉增强是否可用于指导新皮质的功能重组并优化感觉介导的行为。将在三个发育里程碑之一进行操作：1）在视网膜神经节细胞轴突进入间脑之前和丘脑皮质传入神经到达皮质之前。 2）在睁眼之前，在丘脑皮质传入神经支配新皮质之后，但在轴突修剪和皮质发育完成之前。 3) 眼睛刚睁开后，离视网膜和丘脑皮质发育已建立，并且脑室下区和所有六个皮质层均已出现。这些动物将暴露于正常或触觉（对于双侧去核）或视觉（对于皮质病变）增强的环境。我们的动物模型，短尾负鼠（Monodelphis Domestica）是早产的，允许在发育时间点对神经系统进行宫外操作，而这在其他哺乳动物的子宫内是可以进行的。动物成熟后，我们将使用行为测试结合电生理学和神经解剖学技术来检查感觉辨别、重组皮质的功能组织和神经反应特性、皮质和丘脑的连接性以及细胞组成，包括神经元数量和密度。重新组织皮质。这些研究在范围上是新颖的，提供了一个机会，可以将在细胞和系统水平上获得的详细知识转化为重要的治疗干预措施，旨在指导多感觉可塑性，并优化视力丧失后的感觉介导的行为。