Experience-dependent Cellular Plasticity Mechanisms

大脑活动对于神经元和回路的发育和可塑性至关重要，然而， 对活动产生功能回路的机制的理解是不完整的。这种缺乏 知识阻碍了我们利用活动依赖机制来促进电路的能力， 可塑性可塑性诱导刺激诱导神经元蛋白质动力学，包括调节性增加， 蛋白质合成减少。我们最近进行了定量体内蛋白质组学分析， 确定了非洲爪蟾蝌蚪视觉系统中新合成蛋白质的变化， 可塑性诱导的视觉刺激。我们确定了许多候选可塑性蛋白（CPP），包括 其中一些调节蛋白质合成，而另一些则具有不同的细胞和突触功能。这里 我们将探索可塑性诱导刺激启动蛋白质合成依赖性级联反应的模型， 事件，从上游翻译调节因子的从头合成开始， 调节不同效应蛋白的合成，在视觉经验依赖的电路可塑性在非洲爪蟾， 使用蛋白质组学、电生理学、体内结构和功能成像以及行为测定。 经典研究揭示了中枢神经系统损伤后的电路重连事件。我们已经证明 视顶盖的局部损伤损害了爪蟾的视觉回避行为， 具有短暂视觉体验的动物有助于受损回路的恢复。为了探索灵活性 经验依赖的可塑性机制，我们将测试是否新合成的候选可塑性 蛋白质是受损视觉回路依赖视觉经验的康复所必需的。 这些实验的结果可以确定新的机制，有助于经验依赖性 神经系统发育中的可塑性。

Brain activity is essential for the development and plasticity of neurons and circuits, however our understanding of the mechanisms by which activity generates functional circuits is incomplete. This lack of knowledge impedes our ability to take advantage of activity-dependent mechanisms to facilitate circuit plasticity. Plasticity-inducing stimuli induce neuronal protein dynamics, including regulated increases and decreases in protein synthesis. We recently conducted a quantitative in vivo proteomic analysis which identified changes in newly synthesized proteins in the Xenopus tadpole visual system in response to plasticity-inducing visual stimulation. We identified numerous candidate plasticity proteins (CPPs), including several that regulate protein synthesis, whereas others have diverse cellular and synaptic functions. Here we will probe the model that plasticity-inducing stimuli initiate a cascade of protein synthesis-dependent events, beginning with de novo synthesis of upstream translational regulators and culminating in the regulated synthesis of diverse effector proteins, in visual experience dependent circuit plasticity in Xenopus, using proteomics, electrophysiology, in vivo structural and functional imaging, and behavioral assays. Classical studies have revealed circuit-rewiring events in response to CNS damage. We have shown that local damage to the optic tectum impairs visual avoidance behavior in Xenopus and that treating injured animals with brief bouts of visual experience facilitates recovery of the injured circuit. To probe the flexibility of experience-dependent plasticity mechanisms, we will test whether newly synthesized candidate plasticity proteins are required for the visual experience-dependent rehabilitation of the injured visuomotor circuit. Results of these experiments may identify novel mechanisms contributing to experience-dependent plasticity in developing nervous systems.