Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes

Parvalbumin-expressing (PV+) basket cells are fast-spiking interneurons that exert critical control over local neuronal circuit activity and oscillations. PV+ interneuron axons are partially myelinated but the electrical and metabolic roles of myelin in axonal functions remain poorly understood. Here, we developed Cre-dependent AAV vectors for cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions and mining of ultrastructural data revealed that mitochondria selectively cluster to myelinated segments of PV+ basket cell axons. Cuprizone-induced demyelination abolished mitochondrial clustering in PV+ axons but increased axonal mitochondrial densities in excitatory axons. The internodal clustering of mitochondria was preserved with genetic deletion of myelin basic protein, suggesting that noncompacted myelin is sufficient. Finally, two-photon imaging of action potential-evoked mitochondrial calcium (mt-Ca2+) responses showed that internodal mitochondria did not contribute in buffering activity-dependent Ca2+ influx. These findings suggest that oligodendrocyte-PV+ axon signaling assembles mitochondria to branch selectively fine-tune metabolic demands.