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A critical role for purinergic signalling in the mechanisms underlying generation of BOLD fMRI responses
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Wells, J. A., Christie, I. N., Hosford, P. S., Huckstepp, Robert T. R., Angelova, P. R., Vihko, P., Cork, S. C., Abramov, A. Y., Teschemacher, A. G., Kasparov, S., Lythgoe, M. F. and Gourine, A. V. (2015) A critical role for purinergic signalling in the mechanisms underlying generation of BOLD fMRI responses. Journal of Neuroscience, 35 (13). pp. 5284-5292. doi:10.1523/JNEUROSCI.3787-14.2015 ISSN 0270-6474.
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Official URL: http://dx.doi.org/10.1523/JNEUROSCI.3787-14.2015
Abstract
The mechanisms of neurovascular coupling underlying generation of BOLD fMRI signals remain incompletely understood. It has been proposed that release of vasoactive substances by astrocytes couples neuronal activity to changes in cerebrovascular blood flow. However, the role of astrocytes in fMRI responses remains controversial. Astrocytes communicate via release of ATP, and here we tested the hypothesis that purinergic signaling plays a role in the mechanisms underlying fMRI. An established fMRI paradigm was used to trigger BOLD responses in the forepaw region of the somatosensory cortex (SSFP) of an anesthetized rat. Forepaw stimulation induced release of ATP in the SSFP region. To interfere with purinergic signaling by promoting rapid breakdown of the vesicular and/or released ATP, a lentiviral vector was used to express a potent ectonucleotidase, transmembrane prostatic acid phosphatase (TMPAP), in the SSFP region. TMPAP expression had no effect on resting cerebral blood flow, cerebrovascular reactivity, and neuronal responses to sensory stimulation. However, TMPAP catalytic activity markedly reduced the magnitude of BOLD fMRI responses triggered in the SSFP region by forepaw stimulation. Facilitated ATP breakdown could result in accumulation of adenosine. However, blockade of A1 receptors had no effect on BOLD responses and did not reverse the effect of TMPAP. These results suggest that purinergic signaling plays a significant role in generation of BOLD fMRI signals. We hypothesize that astrocytes activated during periods of enhanced neuronal activity release ATP, which propagates astrocytic activation, stimulates release of vasoactive substances and dilation of cerebral vasculature.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Journal or Publication Title: | Journal of Neuroscience | ||||||||
Publisher: | Society for Neuroscience | ||||||||
ISSN: | 0270-6474 | ||||||||
Official Date: | 2015 | ||||||||
Dates: |
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Volume: | 35 | ||||||||
Number: | 13 | ||||||||
Page Range: | pp. 5284-5292 | ||||||||
DOI: | 10.1523/JNEUROSCI.3787-14.2015 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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