Critical Period Plasticity and Binocular Matching in the Visual Cortex

视觉皮层的关键期可塑性和双眼匹配

• 批准号: 7948969
• 负责人: Jianhua Cang
• 金额: $ 27.75万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7948969
• 关键词: Adult; Amblyopia; Architecture; Biological Models; Birth; Calcium; Cells; Clinical; Cortical Blindness; Data; Development; Disease; Eye; Eyelid structure; Goals; Grant; Human; Image; Individual; Life; Mediating; Mental Retardation; Mental disorders; Molecular; Mus; N-Methyl-D-Aspartate Receptors; Nervous System Physiology; Nervous system structure; Neurologic; Neurons; Ocular Dominance; Pattern; Perception; Physiological; Plastics; Process; Property; Receptor Activation; Research; Research Personnel; Role; Seizures; Sensory; Shapes; Staging; Strabismus; Structure; Synapses; Synaptic plasticity; System; Testing; Time; Vision; Visual; Visual Cortex; Visual system structure; Whole-Cell Recordings; Work; abstracting; base; brain shape; critical period; experience; in vivo; insight; juvenile animal; meetings; monocular; monocular deprivation; neural circuit; neurodevelopment; orientation selectivity; postsynaptic; receptive field; research study; response; spatiotemporal; synaptic inhibition; time orientation; transmission process; two-photon; vision development; visual deprivation; visual information

DESCRIPTION (provided by applicant): Optimal functioning of the nervous system requires selective wiring of neural circuits, the precision of which is achieved through experience-dependent refinement after birth. A classical model system of the experience-dependent development is the ocular dominance plasticity in the visual system, where monocular eyelid closure in a "critical period" of early life leads to a shift of cortical responses towards the non-deprived eye. Despite decades of work, it is still unknown what purpose the critical period serves during normal development, when the inputs from the two eyes are intact. In this grant, the proposed work aims to determine what cortical function is shaped by normal vision-induced plasticity during the critical period and to reveal its underlying molecular and synaptic mechanisms. First, the investigators will test whether the critical period plasticity drives the matching of binocular orientation preference during normal development. Both single unit recording and two-photon calcium imaging will be performed in the mouse visual cortex to determine the time course of binocular matching of orientation preference and its requirement of normal visual experience in the critical period. Second, with genetically or pharmacologically altered level of inhibition, which is known to shift the timing of the critical period of ocular dominance plasticity, the investigators will determine whether intracortical inhibition controls the timing of binocular matching by regulating the maturation of orientation selectivity. Intracellular whole cell recording will also be performed in vivo to reveal the spatiotemporal patterns of synaptic inhibition in mediating the binocular matching of orientation preference and in regulating the critical period timing. Finally, the receptive field structure of individual cortical neurons will be studied separately to the two eyes at different developmental stages to reveal how receptive fields change monocularly during the critical period to mediate binocular matching of orientation preference. Pharmacological experiments will also be carried out to determine if cortical activity and NMDA receptor activation are required for the binocular matching process. Together, these studies will reveal a physiological role for the critical period in normal development. Because ocular dominance plasticity and its critical period is a model system for human amblyopia and strabismus, a full understanding of cortical changes that normally take place during development will have important implications for the understanding and treatment of these diseases. PUBLIC HEALTH RELEVANCE: The long-term goal of our research is to reveal the function and development of precise connections between neurons in the nervous system. These studies are of great clinical importance, because many neurological and psychiatric disorders result from miswiring of synaptic connections, such as cortical blindness, seizure, and mental retardation. Our studies will thus contribute to the understanding and treatment of these disorders.

描述(申请人提供)：神经系统的最佳功能需要选择性地连接神经回路，其精确度是通过出生后依赖经验的改进而实现的。经验依赖发展的经典模型系统是视觉系统中的眼优势可塑性，在早期生命的关键时期，单眼眼皮闭合导致皮质反应向非剥夺眼转移。尽管经过了几十年的研究，但在正常发育过程中，当两只眼睛的输入完好无损时，关键时期的作用仍然是未知的。在这项拨款中，拟议的工作旨在确定在关键时期正常视觉诱导的可塑性对大脑皮质功能的影响，并揭示其潜在的分子和突触机制。首先，研究人员将检验在正常发育过程中，关键期可塑性是否会驱动双眼定向偏好的匹配。在小鼠视皮层进行单单位记录和双光子钙成像，以确定双眼定向偏好匹配的时间进程及其在关键期对正常视觉体验的要求。其次，通过基因或药物改变的抑制水平，已知会改变眼睛优势可塑性关键期的时间，研究人员将确定皮质内抑制是否通过调节定向选择性的成熟来控制双眼匹配的时间。还将在体内进行细胞内全细胞记录，以揭示突触抑制在调节定向偏好的双眼匹配和调节临界期计时方面的时空模式。最后，将对不同发育阶段的双眼分别研究单个皮质神经元的感受野结构，以揭示在关键期如何单眼改变感受野来调节定向偏好的双眼匹配。还将进行药理学实验，以确定双眼配对过程是否需要皮质活动和NMDA受体激活。总而言之，这些研究将揭示正常发育关键期的生理作用。由于眼优势可塑性及其关键期是人类弱视和斜视的一个模型系统，充分了解发育过程中正常发生的皮质变化对于了解和治疗这些疾病具有重要意义。 公共卫生相关性：我们研究的长期目标是揭示神经系统中神经元之间精确连接的功能和发展。这些研究具有重要的临床意义，因为许多神经和精神疾病是由突触连接的错误连接引起的，如皮质失明、癫痫和智力低下。因此，我们的研究将有助于理解和治疗这些疾病。