Distal activity patterns shape the spatial specificity of neurovascular coupling

Neurovascular coupling links brain activity to local changes in blood flow, forming the basis for non-invasive brain mapping. Using multiscale imaging, we investigated how vascular activity spatially relates to neuronal activity elicited by single whiskers across different columns and layers of mouse cortex. Here we show that mesoscopic hemodynamic signals quantitatively reflect neuronal activity across space but are composed of a highly heterogeneous pattern of responses across individual vessel segments that is poorly predicted by local neuronal activity. Rather, this heterogeneity is dependent on vessel directionality, specifically in thalamocortical input layer 4, where capillaries respond preferentially to neuronal activity patterns along their downstream perfusion domain. Thus, capillaries fine-tune blood flow based on distant activity and encode laminar-specific activity patterns. These findings imply that vascular anatomy sets a resolution limit on functional imaging signals, where individual blood vessels inaccurately report neuronal activity in their immediate vicinity but, instead, integrate activity patterns along the vascular arbor. The spatial relationship between neuronal and vascular activity remains highly debated. In this study, the authors used multiscale optical imaging to show how vascular architecture limits the spatial specificity of neurovascular coupling.