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