Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes.

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 (Ca 2+ ) responses showed that interneuron myelination attenuates both the cytosolic and mitochondrial Ca 2+ transients. These findings suggest that oligodendrocyte ensheathment of PV + axons assembles mitochondria to branch selectively fine-tune metabolic demands.