3D optogenetic control of arteriole diameter in vivo

Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotempor...

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Main Authors: Philip J O'Herron, David A Hartmann, Kun Xie, Prakash Kara, Andy Y Shih
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/72802
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author Philip J O'Herron
David A Hartmann
Kun Xie
Prakash Kara
Andy Y Shih
author_facet Philip J O'Herron
David A Hartmann
Kun Xie
Prakash Kara
Andy Y Shih
author_sort Philip J O'Herron
collection DOAJ
description Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.
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spelling doaj.art-5bd7287947e74030b7fa2e6f069170042022-12-22T03:24:56ZengeLife Sciences Publications LtdeLife2050-084X2022-09-011110.7554/eLife.728023D optogenetic control of arteriole diameter in vivoPhilip J O'Herron0https://orcid.org/0000-0002-8137-9432David A Hartmann1Kun Xie2Prakash Kara3https://orcid.org/0000-0002-4285-1634Andy Y Shih4Department of Physiology, Augusta University, Augusta, United States; Department of Neuroscience, Medical University of South Carolina, Charleston, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, United States; Department of Neurology & Neurological Sciences, Stanford University, Stanford, United StatesDepartment of Physiology, Augusta University, Augusta, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, United States; Department of Neuroscience, University of Minnesota, Minneapolis, United States; Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, United StatesDepartment of Neuroscience, Medical University of South Carolina, Charleston, United States; Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, United States; Department of Bioengineering, University of Washington, Seattle, United States; Department of Pediatrics, University of Washington, Seattle, United StatesModulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.https://elifesciences.org/articles/72802optogeneticsvasculartwo-photonblood flow
spellingShingle Philip J O'Herron
David A Hartmann
Kun Xie
Prakash Kara
Andy Y Shih
3D optogenetic control of arteriole diameter in vivo
eLife
optogenetics
vascular
two-photon
blood flow
title 3D optogenetic control of arteriole diameter in vivo
title_full 3D optogenetic control of arteriole diameter in vivo
title_fullStr 3D optogenetic control of arteriole diameter in vivo
title_full_unstemmed 3D optogenetic control of arteriole diameter in vivo
title_short 3D optogenetic control of arteriole diameter in vivo
title_sort 3d optogenetic control of arteriole diameter in vivo
topic optogenetics
vascular
two-photon
blood flow
url https://elifesciences.org/articles/72802
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AT davidahartmann 3doptogeneticcontrolofarteriolediameterinvivo
AT kunxie 3doptogeneticcontrolofarteriolediameterinvivo
AT prakashkara 3doptogeneticcontrolofarteriolediameterinvivo
AT andyyshih 3doptogeneticcontrolofarteriolediameterinvivo