UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses

Wells, JA; Christie, IN; Hosford, PS; Huckstepp, RTR; Angelova, PR; Vihko, P; Cork, SC; ... Gourine, AV; + view all (2015) A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses. Journal of Neuroscience , 35 (13) pp. 5284-5292. 10.1523/JNEUROSCI.3787-14.2015. Green open access

[thumbnail of Wells_5284.full.pdf]
Preview
Text
Wells_5284.full.pdf - Published Version

Download (1MB) | Preview

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.

Type: Article
Title: A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.3787-14.2015
Publisher version: http://dx.doi.org/10.1523/JNEUROSCI.3787-14.2015
Language: English
Additional information: This work is available to the public to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. Copyright © 2015 the authors
Keywords: Science & technology, life sciences & biomedicine, neurosciences, neurosciences & neurology, astrocyte, atp, bold, fmri, glia, neurovascular coupling, cerebral-blood-flow, prostatic-acid-phosphatase, cortex in-vivo, somatosensory cortex, functional activation, alpha-chloralose, calcium dynamics, nervous-system, mouse cortex, atp release.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1465207
Downloads since deposit
71Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item