CO2 signaling mediates neurovascular coupling in the cerebral cortex

Patrick S. Hosford; Jack A. Wells; Shereen Nizari; Isabel N. Christie; Shefeeq M. Theparambil; Pablo A. Castro; Anna Hadjihambi; L. Felipe Barros; Iván Ruminot; Mark F. Lythgoe; Alexander V. Gourine

doi:10.1038/s41467-022-29622-9

CO₂ signaling mediates neurovascular coupling in the cerebral cortex

Patrick S. Hosford^*, Jack A. Wells, Shereen Nizari, Isabel N. Christie, Shefeeq M. Theparambil, Pablo A. Castro, Anna Hadjihambi, L. Felipe Barros, Iván Ruminot^*, Mark F. Lythgoe, Alexander V. Gourine^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO₂-sensitive vasodilatory brain mechanism with surplus of exogenous CO₂ or disruption of brain CO₂/HCO₃⁻ transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO₂ and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO₂ mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity.

Original language	English
Article number	2125
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29622-9
State	Published - 2022

Bibliographical note

Funding Information:
This work was supported by The Wellcome Trust (A.V.G.; refs: 200893 and 223057), Fondecyt Iniciación Grant 11190678 (I.R.) and ANID-BMBF 180045 grant (L.F.B.). A.V.G. was supported by Wellcome Senior Research Fellowship (ref: 200893). J.A.W. was supported by Wellcome Trust/Royal Society Sir Henry Dale Fellowship (ref: 204624). CECs is funded by the Chilean Government through the Centers of Excellence Base Financing Program. We thank Professor Gary E. Shull (Cincinnati, USA) for providing NBCe1 mice and Professor Frank Kirchhoff (Hamburg, Germany) for providing GLAST-CRE ERT2 mice. We thank Dr Bredford Kerr (Santiago, Chile) for his help in running the behavioural studies. We are also grateful to Professor David Attwell for his comments on the first version of the manuscript. flox/flox

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-022-29622-9

Cite this

@article{36ae4913dd4a47a4bdf06c8b487b4ce8,

title = "CO2 signaling mediates neurovascular coupling in the cerebral cortex",

abstract = "Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3− transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity.",

author = "Hosford, {Patrick S.} and Wells, {Jack A.} and Shereen Nizari and Christie, {Isabel N.} and Theparambil, {Shefeeq M.} and Castro, {Pablo A.} and Anna Hadjihambi and Barros, {L. Felipe} and Iv{\'a}n Ruminot and Lythgoe, {Mark F.} and Gourine, {Alexander V.}",

note = "Funding Information: This work was supported by The Wellcome Trust (A.V.G.; refs: 200893 and 223057), Fondecyt Iniciaci{\'o}n Grant 11190678 (I.R.) and ANID-BMBF 180045 grant (L.F.B.). A.V.G. was supported by Wellcome Senior Research Fellowship (ref: 200893). J.A.W. was supported by Wellcome Trust/Royal Society Sir Henry Dale Fellowship (ref: 204624). CECs is funded by the Chilean Government through the Centers of Excellence Base Financing Program. We thank Professor Gary E. Shull (Cincinnati, USA) for providing NBCe1 mice and Professor Frank Kirchhoff (Hamburg, Germany) for providing GLAST-CRE ERT2 mice. We thank Dr Bredford Kerr (Santiago, Chile) for his help in running the behavioural studies. We are also grateful to Professor David Attwell for his comments on the first version of the manuscript. flox/flox Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-29622-9",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - CO2 signaling mediates neurovascular coupling in the cerebral cortex

AU - Hosford, Patrick S.

AU - Wells, Jack A.

AU - Nizari, Shereen

AU - Christie, Isabel N.

AU - Theparambil, Shefeeq M.

AU - Castro, Pablo A.

AU - Hadjihambi, Anna

AU - Barros, L. Felipe

AU - Ruminot, Iván

AU - Lythgoe, Mark F.

AU - Gourine, Alexander V.

N1 - Funding Information: This work was supported by The Wellcome Trust (A.V.G.; refs: 200893 and 223057), Fondecyt Iniciación Grant 11190678 (I.R.) and ANID-BMBF 180045 grant (L.F.B.). A.V.G. was supported by Wellcome Senior Research Fellowship (ref: 200893). J.A.W. was supported by Wellcome Trust/Royal Society Sir Henry Dale Fellowship (ref: 204624). CECs is funded by the Chilean Government through the Centers of Excellence Base Financing Program. We thank Professor Gary E. Shull (Cincinnati, USA) for providing NBCe1 mice and Professor Frank Kirchhoff (Hamburg, Germany) for providing GLAST-CRE ERT2 mice. We thank Dr Bredford Kerr (Santiago, Chile) for his help in running the behavioural studies. We are also grateful to Professor David Attwell for his comments on the first version of the manuscript. flox/flox Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3− transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity.

AB - Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3− transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity.

UR - http://www.scopus.com/inward/record.url?scp=85128411582&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-29622-9

DO - 10.1038/s41467-022-29622-9

M3 - Article

C2 - 35440557

AN - SCOPUS:85128411582

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2125

ER -