Vaccaro Victoria, Devine Michael J, Higgs Nathalie F, Kittler Josef T
Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
EMBO Rep. 2017 Feb;18(2):231-240. doi: 10.15252/embr.201642710. Epub 2016 Dec 30.
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 Ca indicator, SyGCaMP5, to address whether presynaptic Ca responses are altered by mitochondria in synaptic terminals. We find that presynaptic Ca 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 Ca-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 Ca 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.
线粒体运输受神经元活动影响，但线粒体定位如何影响神经元传递和可塑性仍不清楚。在这里，我们使用对基因编码的突触前靶向钙指示剂SyGCaMP5进行活细胞成像，以研究突触终末中的线粒体是否会改变突触前钙反应。我们发现，含有线粒体的终末中，突触前钙信号以及神经递质释放均显著降低。此外，在长期活动变化过程中，突触前部位线粒体的定位可发生改变，这取决于线粒体运输蛋白Miro1的钙传感功能。另外，我们发现Miro1介导的线粒体活动依赖性突触重新定位使神经元能够根据神经元活动的长期变化，通过稳态调节改变突触前钙信号的强度。我们的结果支持这样一种模型，即线粒体在神经元活动增强期间被招募到突触前终末，并在稳态可塑性过程中参与调整突触信号。
