Miro1-dependent mitochondrial positioning drives the rescaling of presynaptic Ca2+ signals during homeostatic plasticity.
Miro1-dependent mitochondrial positioning drives the rescaling of presynaptic Ca2+ signals during homeostatic plasticity.
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DOI：
10.15252/embr.201642710
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发表时间：
2017-02
期刊：
影响因子：
7.7
通讯作者：
Kittler JT
中科院分区：
文献类型：
--
作者：
Vaccaro V;Devine MJ;Higgs NF;Kittler JT
线粒体的运输受到神经元活动的影响，但线粒体的位置如何影响神经元的传递和可塑性仍不清楚。在这里，我们使用基因编码的突触前靶向钙指示剂SyGCaMP5的活细胞成像来研究突触前钙反应是否被突触终末中的线粒体改变。我们发现，在含有线粒体的终末，突触前钙信号以及神经递质释放显著减少。此外，线粒体在突触前部位的定位可以在长期活动变化期间改变，这取决于线粒体运输蛋白Miro1的钙传感功能。此外，我们发现，Miro1介导的线粒体活性依赖的突触重新定位允许神经元对突触前钙信号的强度进行动态平衡改变，以响应神经元活动的长期变化。我们的结果支持这样一个模型，即在神经元活动增强的时期，线粒体被招募到突触前终末，并参与在稳态可塑性期间重新调整突触信号。
Mitochondrial trafficking is influenced by neuronal activity, but it remains unclear how mitochondrial positioning influences neuronal transmission and plasticity. Here, we use live cell imaging with the genetically encoded presynaptically targeted Ca2+ indicator, SyGCaMP5, to address whether presynaptic Ca2+ responses are altered by mitochondria in synaptic terminals. We find that presynaptic Ca2+ signals, as well as neurotransmitter release, are significantly decreased in terminals containing mitochondria. Moreover, the localisation of mitochondria at presynaptic sites can be altered during long‐term activity changes, dependent on the Ca2+‐sensing function of the mitochondrial trafficking protein, Miro1. In addition, we find that Miro1‐mediated activity‐dependent synaptic repositioning of mitochondria allows neurons to homeostatically alter the strength of presynaptic Ca2+ signals in response to prolonged changes in neuronal activity. Our results support a model in which mitochondria are recruited to presynaptic terminals during periods of raised neuronal activity and are involved in rescaling synaptic signals during homeostatic plasticity.