Miro1-dependent mitochondrial dynamics in parvalbumin interneurons.
Miro1-dependent mitochondrial dynamics in parvalbumin interneurons.
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DOI：
10.7554/elife.65215
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发表时间：
2021-06-30
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：
Kontou G;Antonoudiou P;Podpolny M;Szulc BR;Arancibia-Carcamo IL;Higgs NF;Lopez-Domenech G;Salinas PC;Mann EO;Kittler JT
线粒体的时空分布对于支持神经元信号传导所需的精确ATP供应和钙缓冲至关重要。表达小清蛋白（PV+）的快速尖峰GABA能中间神经元具有高线粒体含量，反映了它们的大能量利用。在抑制性神经元中，正确的运输和精确的线粒体定位的重要性仍然没有得到很好的阐明。Miro 1是一种Ca 2+感应衔接蛋白，将线粒体连接到运输装置，用于沿着轴突和树突进行微管依赖性运输，以满足细胞的代谢和Ca 2+缓冲需求。在这里，我们探讨了Miro 1在PV+中间神经元中的作用，以及线粒体运输的变化如何改变小鼠大脑中的网络活动。通过采用实时和固定成像，我们发现PV+中间神经元中Miro 1定向运输的损伤改变了它们的线粒体分布和轴突分支，而PV+中间神经元介导的抑制保持不变。这些变化伴随着离体海马γ振荡（30-80 Hz）频率的增加，并促进了抗焦虑作用。我们的研究结果表明，PV+ interneurons中线粒体动力学的精确调节对于适当的神经元信号传导和网络同步至关重要。
The spatiotemporal distribution of mitochondria is crucial for precise ATP provision and calcium buffering required to support neuronal signaling. Fast-spiking GABAergic interneurons expressing parvalbumin (PV+) have a high mitochondrial content reflecting their large energy utilization. The importance for correct trafficking and precise mitochondrial positioning remains poorly elucidated in inhibitory neurons. Miro1 is a Ca²+-sensing adaptor protein that links mitochondria to the trafficking apparatus, for their microtubule-dependent transport along axons and dendrites, in order to meet the metabolic and Ca2+-buffering requirements of the cell. Here, we explore the role of Miro1 in PV+ interneurons and how changes in mitochondrial trafficking could alter network activity in the mouse brain. By employing live and fixed imaging, we found that the impairments in Miro1-directed trafficking in PV+ interneurons altered their mitochondrial distribution and axonal arborization, while PV+ interneuron-mediated inhibition remained intact. These changes were accompanied by an increase in the ex vivo hippocampal γ-oscillation (30–80 Hz) frequency and promoted anxiolysis. Our findings show that precise regulation of mitochondrial dynamics in PV+ interneurons is crucial for proper neuronal signaling and network synchronization.