Axons organize into micro-tracts around the cortical vasculature

Neural activity is metabolically costly and supported by local increases in cerebral blood flow. The process by which neural activity drives blood flow increase, neurovascular coupling (NVC), remains poorly understood. One persistent knowledge gap is how subcellular compartments are arranged at the vascular wall, where local signaling occurs. This requires a survey of the neurovascular interface at the nanometer scale. To this end, we analyzed a ~1 mm3 volume of mouse visual cortex imaged with serial electron microscopy. We manually labeled different vascular zones, and classified the EM segments surrounding hundreds of vessel segments across these zones. We found that capillaries and venous vessels are surrounded by more axonal volume than arteriolar vessels. Perivascular axons tended to bundle into micro-tracts, where axons ran in parallel and coursed near the vessel wall in a variety of geometric orientations. Micro-tracts cover ~60% of the surface of capillaries, but only 24-40% of every other vascular zone's surface. Finally, we show that the extensive axon arbors of basket cell inhibitor neurons are within micro-tracts. Their axons come in closest proximity to vessels, and on average, approach 2 to 3 fold more vessel segments than other neuronal subtypes. Altogether, perivascular axonal micro-tracts may be an important physical substrate for NVC signaling at capillaries.