eLife | |
Miro1-dependent mitochondrial dynamics in parvalbumin interneurons | |
Patricia C Salinas1  Marina Podpolny1  Guillermo Lopez-Domenech2  Georgina Kontou2  Nathalie F Higgs2  I Lorena Arancibia-Carcamo2  Blanka R Szulc2  Josef T Kittler2  Pantelis Antonoudiou3  Edward O Mann4  | |
[1] Department of Cell and Developmental Biology, University College London, London, United Kingdom;Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom;Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom;Oxford Ion Channel Initiative, University of Oxford, Oxford, United Kingdom; | |
关键词: mitochondrial trafficking; parvalbumin interneurons; gamma oscillations; Mouse; | |
DOI : 10.7554/eLife.65215 | |
来源: eLife Sciences Publications, Ltd | |
【 摘 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.
【 授权许可】
CC BY
【 预 览 】
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RO202107232643873ZK.pdf | 6280KB | download |