Miro1-dependent mitochondrial dynamics in parvalbumin interneurons.
Autor: | Kontou G; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom., Antonoudiou P; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom., Podpolny M; Department of Cell and Developmental Biology, University College London, London, United Kingdom., Szulc BR; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom., Arancibia-Carcamo IL; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom., Higgs NF; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom., Lopez-Domenech G; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom., Salinas PC; Department of Cell and Developmental Biology, University College London, London, United Kingdom., Mann EO; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.; Oxford Ion Channel Initiative, University of Oxford, Oxford, United Kingdom., Kittler JT; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. |
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Jazyk: | angličtina |
Zdroj: | ELife [Elife] 2021 Jun 30; Vol. 10. Date of Electronic Publication: 2021 Jun 30. |
DOI: | 10.7554/eLife.65215 |
Abstrakt: | 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 Ca 2+ -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. Competing Interests: GK, PA, MP, BS, IA, NH, GL, PS, EM, JK No competing interests declared (© 2021, Kontou et al.) |
Databáze: | MEDLINE |
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