Pericyte connectome: spatial precision of neurovascular coupling is driven by discriminatory connectivity maps of pericytes and endothelial cells and is disrupted in disease

Tamas Kovacs-Oller, Elena Ivanova, Paola Bianchimano, Botir T. Sagdullaev

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Nov 15, 2019
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Received Date: 6th November 19

Functional hyperemia, or matching blood flow to activity, is spatially accurate to direct the oxygen and nutrients to regionally firing neurons. The underlying signaling mechanisms of neurovascular coupling remain unclear, but are critical for brain function and establish the diagnostic power of BOLD-fMRI. Here, we described a mosaic of pericytes, the vasomotor capillary cells in the living retina. We then tested if this symmetric net of pericytes and surrounding neuroglia predicted a connectivity map in response to sensory stimuli. Surprisingly, we found that these connections were not only discriminatory 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 discriminatory nature 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 microvascular disease.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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