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）：了解如何在皮层中创建神经元电路的基础是定义将电活动传递到神经元和连接的结构变化的机制。原发性视觉皮层（V1）已成为描述发育过程中活性依赖性可塑性的现象和机制的探索基础。在V1中，眼部优势可塑性，尤其是在早期，定义明确的关键时期，是理解视觉活动引发的功能和结构变化的模型。我们建议在关键时期定义快速功能可塑性的结构相关性；在这样做时，我们试图了解将功能驱动器依次转移到树突和轴突末端的结构变化的机制。特别是，刺是皮质中绝大多数兴奋性突触的部位，它们的结构与完整皮质中功能可塑性的关系几乎是未知的。我们将使用固有信号光学成像，高分辨率两光子激光扫描显微镜在体内和体外扫描显微镜，以及在雪貂和小鼠中的外源蛋白的病毒表达，以检查：（1）雪质塑料量的关键视觉统治期间，雪质纯皮的功能变化的时间过程； （2）雪貂视觉皮层快速功能变化的结构相关性； （3）在雪貂视觉皮层中突触驱动变化的棘突的结构变化； （4）短期和长期期视觉剥夺后，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，涉及将功能变化转化为视觉皮层中结构重组的功能。这些实验将共同研究视觉皮层中单个突触时结构变化的范围和时间过程，并揭示其通过视觉调节动态调节的机制。此类信息对于解释皮质发育的病理和提出治疗策略至关重要。