Structural correlates of rapid cortical plasticity

快速皮质可塑性的结构相关性

• 批准号: 7751237
• 负责人: MRIGANKA SUR
• 金额: $ 39.65万
• 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 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751237
• 关键词: Actins; Address; Affect; Alteplase; Apical; Attention; Axon; Biological Assay; Calcium; Cells; Cytoskeleton; Dendrites; Development; Excitatory Synapse; Extracellular Matrix; Eye; F-Actin; Ferrets; Image; In Vitro; Label; Laser Scanning Microscopy; Lead; Mediating; Modeling; Modification; Molecular; Mus; Neurons; Ocular Dominance; Pathology; Phosphorylation; Photic Stimulation; Photons; Presynaptic Terminals; Proteins; Proteolysis; Pyramidal Cells; Reagent; Recovery; Regulation; Research Personnel; Resolution; Role; Signal Pathway; Signal Transduction; Site; Slice; Structure; Surgical sutures; Synapses; Techniques; Time; Translating; Vertebral column; Viral; Vision; Visual; Visual Cortex; Withdrawal; area striata; base; calmodulin-dependent protein kinase II; cell motility; critical period; deprivation; hippocampal pyramidal neuron; in vivo; monocular; monocular deprivation; novel; optical imaging; polymerization; postsynaptic; receptor expression; release of sequestered calcium ion into cytoplasm; research study; treatment strategy; two-photon; visual deprivation

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.

理解神经元回路如何在皮层中产生的基础是通过以下方式来定义机制： 这种电活动被转换成神经元和连接的结构变化。初级视觉 皮层（V1）一直是描述活动现象和机制的试验场- 发育过程中的可塑性。在V1内，眼优势可塑性，特别是在 早期，定义明确的关键期，是理解功能和结构变化的模型， 视觉活动我们建议定义在关键阶段快速功能可塑性的结构相关性。 期间;在这样做的时候，我们试图了解的机制，顺序重复功能驱动器进入 树突和轴突终末的结构变化。特别是，脊椎是绝大多数动物的栖息地 皮质中的兴奋性突触，以及它们的结构如何与完整皮质中的功能可塑性相关 仍然是个未知数我们将使用固有信号光学成像技术，高分辨率 双光子激光扫描显微镜在体内和体外，和外源蛋白的病毒表达， 雪貂和小鼠，检查：（1）雪貂视觉皮层功能变化的时间过程中， 眼优势可塑性的关键时期;（2）快速功能变化的结构相关性， 雪貂视皮层;（3）雪貂视皮层中具有不同突触驱动的棘的结构变化;（4） 短期和长期视觉刺激后小鼠视觉皮层的功能和结构变化 剥夺，包括不同层和特定细胞类别的变化;（5）特定分子 包括CaMKII、肌动蛋白和细胞外基质的作用，参与翻译 从功能变化到视觉皮层的结构重组。这些实验将 研究在前所未有的细节的程度和时间过程中的结构变化，在单一的突触在 视觉皮层，并揭示其背后的视觉动态调节机制。该等资料不 对于解释皮质发育的病理学和提出治疗策略至关重要。