Structural correlates of rapid cortical plasticity

要了解大脑皮层中神经元回路是如何产生的，最基本的方法是通过 这种电活动被转化为神经元和连接的结构变化。初级视觉 大脑皮层(V1)已经成为描述活动现象和机制的试验场。 发育过程中的依赖可塑性。在V1内，眼睛优势可塑性，特别是在 早期的、定义明确的关键期，是理解由 视觉活动。我们建议在关键时期定义快速功能可塑性的结构相关性。 在这样做的过程中，我们试图理解将功能性驱动力顺序地转化为 树突和轴突终末的结构变化。特别是，脊椎是绝大多数 皮层中的兴奋性突触及其结构如何与完整皮质的功能可塑性相关 几乎仍然是未知的。我们将使用本征信号光学成像技术，高分辨率 体内和体外的双光子激光扫描显微镜和外源蛋白的病毒表达 雪貂和小鼠，以检查：(1)雪貂视觉皮质功能变化的时间进程 眼优势可塑性的关键期；(2)眼球快速功能变化的结构相关性 雪貂视皮层；(3)雪貂视皮层内具有不同突触驱动的棘突的结构变化； 小鼠视皮层在短期和长期视觉后的功能和结构变化 剥夺，包括不同层次和特定细胞类别的变化；(5)特定分子 参与翻译的机制，包括CaMKII、肌动蛋白和细胞外基质的作用 视皮层结构重组的功能变化。总而言之，这些实验将 以前所未有的详细程度检查脑内单个突触的结构变化的程度和时间进程 并揭示了视觉对其进行动态调节的机制。这样的信息是 对于解释皮质发育的病理机制和提出治疗策略至关重要。

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.