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The Pericyte Connectome: Spatial Precision of Neurovascular Coupling Is Driven by Selective Connectivity Maps of Pericytes and Endothelial Cells and Is Disrupted in Diabetes

PUBLICATION: 
Journal Article
Authors: 
Tamas Kovacs-Oller, Elena Ivanova, Paola Bianchimano, Botir T Sagdullaev
Year Published: 
2020
Publisher: 
Cell Discov . 2020 Jun 16;6:39. doi: 10.1038/s41421-020-0180-0. eCollection 2020.
Identifiers: 
PMID: 32566247 | PMCID: PMC7296038 | DOI: 10.1038/s41421-020-0180-0
Abstract on PubMed

Abstract

Functional hyperemia, or the matching of blood flow with activity, directs oxygen and nutrients to regionally firing neurons. The mechanisms responsible for this spatial accuracy remain unclear but are critical for brain function and establish the diagnostic resolution of BOLD-fMRI. Here, we described a mosaic of pericytes, the vasomotor capillary cells in the living retina. We then tested whether this net of pericytes and surrounding neuroglia predicted a connectivity map in response to sensory stimuli. Surprisingly, we found that these connections were not only selective across cell types, but also highly asymmetric spatially. First, pericytes connected predominantly to other neighboring pericytes and endothelial cells, and less to arteriolar smooth muscle cells, and not to surrounding neurons or glia. Second, focal, but not global stimulation evoked a directional vasomotor response by strengthening connections along the feeding vascular branch. This activity required local NO signaling and occurred by means of direct coupling via gap junctions. By contrast, bath application of NO or diabetes, a common microvascular pathology, not only weakened the vascular signaling but also abolished its directionality. We conclude that the exclusivity of neurovascular interactions may thus establish spatial accuracy of blood delivery with the precision of the neuronal receptive field size, and is disrupted early in diabetes.