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中文摘要
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项目总结 神经功能需要重塑和重新连接神经连接,通过 基本过程称为突触可塑性。众所周知,...的力量 神经传递受突触前和突触后反馈信号的调节 神经元,这会导致短期和/或长期的结构适应。然而,几乎没有什么是 知道这一规定是如何发生的。目前的目标是澄清这一缺失 通过探索线粒体新出现的信号作用来实现机械性联系,这些作用包括 维持局部突触功能和可塑性能量需求的细胞器。基座 关于神经元活动决定有氧能量转换速度和 我们假设线粒体释放化学活性氧物种(ROS) ROS控制和定位的线粒体发射调节突触功能 和可塑性。我们的初步数据显示,线粒体ROS的释放可以是 在体内的突触前终末中特异性地被激发。我们将率先使用 用于同步诱导和测量ROS发射的光遗传学 突触功能。将使用超分辨率来探索功能性ROS信号目标 荧光显微镜和质谱仪。重要的是,我们的合作者和我们 建立了一种在短短几个小时内诱导和研究突触可塑性的方法 活体的光遗传学。我们的结果将影响旨在改善神经元的治疗 老年性神经退行性变中的沟通。
英文摘要
PROJECT SUMMARY Neuronal function requires the reshaping and rewiring of neural connections through a fundamental process named synaptic plasticity. It is well known that the strength of neurotransmission is regulated by feedback signaling between the pre- and postsynaptic neuron, which leads to short- and/or long-term structural adaptations. However, little is known about how this regulation occurs. The current objective is to elucidate this missing mechanistic link by exploring emerging signaling roles of mitochondria, which are organelles that sustain the local energy demand of synaptic function and plasticity. Based on the rationale that neuronal activity sets the pace of aerobic energy conversion and of emission of chemically reactive oxygen species (ROS) from mitochondria, we hypothesize that controlled and localized mitochondrial emission of ROS regulates synaptic function and plasticity. Our preliminary data show that emission of mitochondrial ROS can be elicited specifically in presynaptic terminals in vivo. We will pioneer in the use of optogenetics for synchronized induction and measurement of ROS emission during synaptic function. Functional ROS signaling targets will be explored using super resolution fluorescence microscopy and mass spectrometry. Importantly, our collaborators and we established a method to elicit and study synaptic plasticity within just a few hours using optogenetics in vivo. Our results will impact therapies aimed improving neuronal communication in age-related neurodegeneration.
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Retraction or reshaping: dissecting the role of mitochondrial ROS in synaptic plasticity
  • 批准号:
    10408079
  • 项目类别:
  • 资助金额:
    $35.66万
  • 财政年份:
    2020
  • 负责人:
    Pablo M Peixoto
  • 依托单位:
Retraction or reshaping: dissecting the role of mitochondrial ROS in synaptic plasticity
  • 批准号:
    10229370
  • 项目类别:
  • 资助金额:
    $35.36万
  • 财政年份:
    2020
  • 负责人:
    Pablo M Peixoto
  • 依托单位:
海外基金