Letter | Published:

Bidirectional control of CNS capillary diameter by pericytes

Nature volume 443, pages 700704 (12 October 2006) | Download Citation

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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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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.

Author information

Author notes

    • Claire M. Peppiatt
    •  & Clare Howarth

    *These authors contributed equally to this work

Affiliations

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

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

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Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to David Attwell.

Supplementary information

PDF files

  1. 1.

    Supplementary Notes

    This file contains Supplementary Methods and Supplementary Figure and Movie legends.

Videos

  1. 1.

    Supplementary Movie 1

    Electrically-evoked pericyte constriction and propagation of pericyte constriction along retinal capillaries.

  2. 2.

    Supplementary Movie 2

    UTP-evoked constriction of retinal capillaries.

  3. 3.

    Supplementary Movie 3

    Noradrenaline-evoked constriction and glutamate-evoked dilation in a molecular layer capillary in a cerebellar slice.

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DOI

https://doi.org/10.1038/nature05193

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