Imaging Synaptic Plasticity in the Visual Cortex in Vivo

体内视觉皮层突触可塑性成像

• 批准号: 7582239
• 负责人: Joshua Trachtenberg
• 金额: $ 30万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7582239
• 关键词: Adult; Amblyopia; Anatomy; Animals; Apical; Area; Axon; Cells; Chemosensitization; Computer software; Custom; Dendrites; Dendritic Spines; Development; Electrophysiology (science); Eye; Fluorescent Dyes; Goals; Green Fluorescent Proteins; Growth; Image; Label; Laser Scanning Microscopy; Length; Link; Long-Term Depression; Long-Term Potentiation; Longitudinal Studies; Macular degeneration; Maps; Measurement; Measures; Molecular; Mus; Neurons; Ocular Dominance; Photons; Physiological; Play; Positioning Attribute; Preparation; Research Personnel; Resolution; Role; Scotoma; Sensory; Series; Signal Transduction; Silicones; Slice; Sorting - Cell Movement; Stimulus; Stroke; Structure; Synapses; Synaptic plasticity; Testing; Therapeutic; Time; Transgenes; Transgenic Mice; Vertebral column; Visual Cortex; Writing; area striata; base; cell type; critical period; density; depressed; depression; deprivation; experience; functional loss; hippocampal pyramidal neuron; in vivo; information processing; monocular; monocular deprivation; neural circuit; novel; optical imaging; postnatal; programs; receptive field; research study; response; synaptogenesis; therapeutic development; tissue fixing; treatment strategy; visual process; visual processing

The experiments proposed in this application investigate the roles of dendritic spine growth and retraction in experience-dependent plasticity in the mouse visual cortex. Recent evidence indicate that dendritic spines are dynamic in the developing and adult cortex: new spines appear daily and grow towards axons to establish novel synapses while some existing spines retract, breaking their synaptic connection. These changes in synaptic connectivity may play important roles in rapidly rewiring cortical circuits during experience-dependent plasticity. The extent to which spine growth and retraction underlie functional changes in cortical circuits will be examined in transgenic mice expressing a green fluorescent protein transgene. 2-photon laser scanning microscopy and intrinsic signal optical imaging will used to repeatedly image spine dynamics and functional changes in cortical ocular dominance in vivo over periods of weeks in the same mice before and after monocular deprivation. By imaging changes in structure and function in the same preparation, it will be possible to determine whether synapse elimination underlies the functional loss of deprived eye inputs and novel synapse formation underlies the gradual strengthening of experienced eye inputs. In vivo electrophysiology and fixed tissue anatomy will be used to determine which cells in which layers are the first to alter their responsiveness and connectivity following monocular deprivation and to map the progression of these changes through the remainder of the cortical circuit. Taken together, these experiments should provide a detailed understanding of the onset and progression of experience-dependent changes in cortical structure and function at the level of receptive fields and synapses. Results from these experiments may aid in the provision of rationally-based therapeutic approaches to amblyopia, scotoma, and stroke.

本申请中提出的实验研究了树突棘生长和收缩在细胞凋亡中的作用。 小鼠视觉皮层的经验依赖性可塑性。最近的证据表明树突棘 在发育和成年的皮层中是动态的：每天都有新的棘出现，并向轴突生长， 建立新的突触，而一些现有的棘回缩，打破它们的突触连接。这些 突触连接的变化可能在大脑皮层回路的快速重布线中起重要作用， 依赖经验的可塑性脊柱生长和回缩的程度是功能性的基础， 将在表达绿色荧光蛋白的转基因小鼠中检查皮质回路的变化 转基因。2-光子激光扫描显微镜和固有信号光学成像将被用于重复 在几周时间内成像脊柱动力学和皮质眼优势在体内的功能变化， 同样的老鼠在单眼剥夺之前和之后。通过成像在结构和功能上的变化， 同样的制备，将有可能确定突触消除是否是功能丧失的基础。 剥夺眼睛输入和新的突触形成的基础上逐步加强经验丰富的眼睛 输入。体内电生理学和固定的组织解剖学将用于确定哪些细胞中， 在单眼剥夺后，各层是第一个改变其反应性和连通性并绘制地图的人 这些变化通过皮层回路的其余部分的进展。综上所述各项 实验应该提供一个详细的了解的发病和进展的经验依赖 皮层结构和功能在感受野和突触水平上的变化。从这些 实验可能有助于提供基于理性的弱视，暗点， 中风