Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes

Koen Kole (), Bas J. B. Voesenek, Maria E. Brinia, Naomi Petersen and Maarten H. P. Kole ()
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Koen Kole: Royal Netherlands Academy of Arts and Sciences
Bas J. B. Voesenek: Royal Netherlands Academy of Arts and Sciences
Maria E. Brinia: Royal Netherlands Academy of Arts and Sciences
Naomi Petersen: Royal Netherlands Academy of Arts and Sciences
Maarten H. P. Kole: Royal Netherlands Academy of Arts and Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Parvalbumin-expressing (PV+) basket cells are fast-spiking inhibitory interneurons that exert critical control over local circuit activity and oscillations. PV+ axons are often myelinated, but the electrical and metabolic roles of interneuron myelination remain poorly understood. Here, we developed viral constructs allowing cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions revealed that mitochondria selectively cluster to myelinated segments of PV+ basket cells, confirmed by analyses of a high-resolution electron microscopy dataset. In contrast to the increased mitochondrial densities in excitatory axons cuprizone-induced demyelination abolished mitochondrial clustering in PV+ axons. Furthermore, with genetic deletion of myelin basic protein the mitochondrial clustering was still observed at internodes wrapped by noncompacted myelin, indicating that compaction is dispensable. Finally, two-photon imaging of action potential-evoked calcium (Ca2+) responses showed that interneuron myelination attenuates both the cytosolic and mitochondrial Ca2+ transients. These findings suggest that oligodendrocyte ensheathment of PV+ axons assembles mitochondria to branch selectively fine-tune metabolic demands.

Date: 2022
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DOI: 10.1038/s41467-022-35350-x

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