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Bidirectional control of CNS capillary diameter by pericytes

Nature volume 443, pages 700–704 (2006)Cite this article

Abstract

Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques1,2,3. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles4, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles5,6, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins7, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at ∼2 µm s-1 to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (γ-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.

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Figure 1: Pericyte anatomy confers flow-regulating capability downstream of arterioles.
Figure 2: Electrical stimulation evokes Ca 2+ -dependent localized constriction of retinal pericytes.
Figure 3: Propagation and transmitter evocation of retinal pericyte constriction.
Figure 4: Effects of neurotransmitters on cerebellar molecular layer capillary and effects of ischaemia on retinal capillary.

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Acknowledgements

We thank C. Auger for initiating the experiments on cerebellar capillaries. This work was supported by the Wellcome Trust, the EU and a Wolfson-Royal Society Award. C.H. is in the 4-year PhD Programme in Neuroscience at UCL.

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  1. Claire M. Peppiatt and Clare Howarth: *These authors contributed equally to this work

Authors and Affiliations

  1. Department of Physiology, University College London, Gower Street, WC1E 6BT, London, UK

    Claire M. Peppiatt, Clare Howarth, Peter Mobbs & David Attwell

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Correspondence to David Attwell.

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Supplementary information

Supplementary Notes

This file contains Supplementary Methods and Supplementary Figure and Movie legends. (PDF 435 kb)

Supplementary Movie 1

Electrically-evoked pericyte constriction and propagation of pericyte constriction along retinal capillaries. (MOV 679 kb)

Supplementary Movie 2

UTP-evoked constriction of retinal capillaries. (MOV 640 kb)

Supplementary Movie 3

Noradrenaline-evoked constriction and glutamate-evoked dilation in a molecular layer capillary in a cerebellar slice. (MOV 1107 kb)

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Peppiatt, C., Howarth, C., Mobbs, P. et al. Bidirectional control of CNS capillary diameter by pericytes. Nature 443, 700–704 (2006). https://doi.org/10.1038/nature05193

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