Miro1-dependent mitochondrial dynamics in parvalbumin interneurons

eLife

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