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（由申请人提供）：神经系统的最佳功能需要选择性的神经回路的接线，其精度是通过出生后通过经验依赖的细化来实现的。经验依赖性发展的经典模型系统是视觉系统中的眼部优势可塑性，在该系统中，在早期的“关键时期”中，单眼眼睑闭合会导致皮质反应向非剥夺眼睛的转变。尽管工作数十年，但当两只眼睛的输入完好无损时，关键时期在正常发育过程中仍有什么目的。在这项赠款中，提出的工作旨在确定在关键时期正常视力诱导的可塑性形成哪种皮质功能，并揭示其潜在的分子和突触机制。首先，研究人员将测试在正常发育过程中，关键时期可塑性是否驱动双眼方向偏好的匹配。单个单元记录和两光子钙成像都将在鼠标视觉皮层中进行，以确定方向偏好的双目匹配时间及其对关键时期正常视觉体验的要求。其次，随着遗传学或药理改变的抑制水平，已知会改变眼部优势可塑性的关键时期的时间，研究人员将通过调节方向选择性的成熟度来确定皮质内抑制是否控制双眼匹配的时间。细胞内的全细胞记录也将在体内进行，以揭示突触抑制的时空模式，以介导方向偏好的双眼匹配和调节关键时期的时机。最后，将在不同发育阶段分别研究单个皮质神经元的接收场结构，以揭示在关键时期内如何单眼变化，以介导方向偏好的双眼匹配。还将进行药理学实验，以确定双眼匹配过程是否需要皮质活性和NMDA受体激活。 总之，这些研究将揭示正常发育中关键时期的生理作用。因为眼优势可塑性及其关键时期是人类弱视和斜视的模型系统，因此对通常在发育过程中通常发生的皮质变化的完全理解将对这些疾病的理解和治疗具有重要意义。 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联系的功能和发展。这些研究非常重要，因为许多神经系统和精神疾病是由于突触连接（例如皮质失明，癫痫发作和智力低下）引起的。因此，我们的研究将有助于对这些疾病的理解和治疗。