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: 8509700
• 负责人: Jianhua Cang
• 金额: $ 33.58万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509700
• 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; 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; base; brain shape; critical period; experience; in vivo; insight; juvenile animal; meetings; monocular; monocular deprivation; nervous system disorder; neural circuit; neurodevelopment; orientation selectivity; postsynaptic; public health relevance; 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.

描述（由申请人提供）：神经系统的最佳功能需要神经回路的选择性布线，其精度是通过出生后的经验依赖性细化来实现的。经验依赖性发展的经典模型系统是视觉系统中的眼优势可塑性，其中单眼眼睑闭合在早期生命的“关键时期”导致皮质反应向非剥夺眼的转移。尽管经过几十年的研究，我们仍然不知道在正常发育过程中，当双眼的输入完好无损时，关键期的作用是什么。在这项资助中，拟议的工作旨在确定在关键时期正常视觉诱导的可塑性塑造了什么样的皮质功能，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，关键期可塑性是否驱动双眼定向偏好的匹配。将在小鼠视皮层进行单单位记录和双光子钙成像，以确定方向偏好的双眼匹配的时间过程及其在关键期的正常视觉经验的要求。第二，与遗传或神经系统改变水平的抑制，这是已知的转移的关键时期的时间的眼优势可塑性，研究人员将确定是否皮质内抑制控制的时间双眼匹配通过调节方向选择性的成熟。还将在体内进行细胞内全细胞记录，以揭示介导定向偏好的双眼匹配和调节关键期定时的突触抑制的时空模式。最后，将研究个体皮层神经元的感受野结构分别对两个眼睛在不同的发展阶段，以揭示如何在单眼感受野变化的关键时期，介导双眼匹配的方向偏好。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模型系统，因此充分了解发育过程中通常发生的皮质变化将对理解和治疗这些疾病具有重要意义。