Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes.

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.