Structural correlates of rapid cortical plasticity

快速皮质可塑性的结构相关性

• 批准号: 7016631
• 负责人: MRIGANKA SUR
• 金额: $ 40.88万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016631
• 关键词: actins; axon; brain electrical activity; brain morphology; calcium flux; calmodulin dependent protein kinase; cell population study; confocal scanning microscopy; dendrites; developmental neurobiology; extracellular matrix; ferrets; genetically modified animals; laboratory mouse; neural information processing; neural plasticity; optics; protein structure function; visual cortex; visual deprivation; visual stimulus

DESCRIPTION (provided by applicant): Fundamental to understanding how neuronal circuits are created in cortex is defining the mechanisms by which electrical activity is transduced into structural changes in neurons and connections. Primary visual cortex (V1) has been a proving ground for describing the phenomena and mechanisms of activity- dependent plasticity during development. Within V1, ocular dominance plasticity, particularly during an early, well-defined critical period, is a model for understanding functional and structural changes initiated by visual activity. We propose to define the structural correlates of rapid functional plasticity during the critical period; in so doing, we seek to understand the mechanisms that sequentially transduce functional drive into structural changes in dendrites and axon terminals. In particular, spines are sites of the vast majority of excitatory synapses in cortex, and how their structure relates to functional plasticity in the intact cortex remains virtually unknown. We will use the techniques of intrinsic signal optical imaging, high resolution two-photon laser scanning microscopy in vivo and in vitro, and viral expression of exogenous proteins, in ferrets and mice, to examine: (1) the time course of functional changes in the ferret visual cortex during the critical period for ocular dominance plasticity; (2) the structural correlates of rapid functional changes in the ferret visual cortex; (3) structural changes in spines with varying synaptic drive in ferret visual cortex; (4) functional and structural changes in the mouse visual cortex following short- and long-term term visual deprivation, including changes in different layers and specific cell classes; (5) specific molecular mechanisms, including the roles of CaMKII, actin and the extracellular matrix, involved in translating functional changes to structural reorganization in the visual cortex. Together, these experiments will examine in unprecedented detail the extent and time course of structural changes at single synapses in the visual cortex, and reveal mechanisms underlying their dynamic regulation by vision. Such information is critical for explaining pathologies of cortical development, and for suggesting strategies for treatment.

描述（由申请人提供）：理解神经元回路如何在皮层中创建的基础是定义电活动转化为神经元和连接的结构变化的机制。初级视觉皮层（V1）已成为描述发育过程中活动依赖性可塑性现象和机制的试验场。在 V1 中，眼优势可塑性，特别是在早期、明确的关键时期，是理解视觉活动引发的功能和结构变化的模型。我们建议定义关键时期快速功能可塑性的结构相关性；在此过程中，我们试图了解将功能驱动依次转换为树突和轴突末端结构变化的机制。特别是，棘是皮层中绝大多数兴奋性突触的所在地，其结构与完整皮层的功能可塑性之间的关系实际上仍然未知。我们将使用内在信号光学成像、体内和体外高分辨率双光子激光扫描显微镜以及雪貂和小鼠中外源蛋白的病毒表达技术来检查：（1）雪貂视觉皮层在眼部优势可塑性的关键时期； (2) 雪貂视觉皮层快速功能变化的结构相关性； (3) 雪貂视觉皮层中突触驱动不同的棘的结构变化； (4)短期和长期视觉剥夺后小鼠视觉皮层的功能和结构变化，包括不同层和特定细胞类别的变化； (5)特定的分子机制，包括CaMKII、肌动蛋白和细胞外基质的作用，参与将功能变化转化为视觉皮层的结构重组。总之，这些实验将以前所未有的细节检查视觉皮层单个突触结构变化的程度和时间过程，并揭示视觉动态调节的潜在机制。这些信息对于解释皮质发育的病理学和建议治疗策略至关重要。