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Precise, 3-D optogenetic control of the diameter of single arterioles

Philip J. O’Herron, David A. Hartmann, Kun Xie, Prakash Kara, Andy Y. Shih
doi: https://doi.org/10.1101/2021.01.29.428609
Philip J. O’Herron
1Department of Physiology, Augusta University, Augusta, Georgia, USA
8Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA
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  • For correspondence: poherron@augusta.edu
David A. Hartmann
2Department of Neurology & Neurological Sciences, Stanford University, Stanford, California, USA
8Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA
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Kun Xie
1Department of Physiology, Augusta University, Augusta, Georgia, USA
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Prakash Kara
3Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA
4Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA
8Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA
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Andy Y. Shih
5Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA
6Department of Pediatrics, University of Washington, Seattle, Washington, USA
7Department of Bioengineering, University of Washington, Seattle, Washington, USA
8Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA
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Abstract

Modulation of brain arteriole diameter is critical for maintenance of cerebral blood pressure and control of hyperemia during regional neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control and monitor blood flow with high spatiotemporal resolution. Here, we describe a new all-optical approach to precisely control and monitor arteriolar contractility in vivo using combined two-photon optogenetics and imaging. The expression of the excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction following brief light pulses. Targeted two-photon activation of ReaCHR using a spatial light modulator (SLM) produced highly localized constrictions when targeted to individual arteries within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient blood flow reductions. Additionally, we show that optogenetic constriction can offset or completely block sensory stimulus evoked vasodilation, providing a valuable tool to dissociate blood flow changes from neural activity.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 31, 2021.
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Precise, 3-D optogenetic control of the diameter of single arterioles
Philip J. O’Herron, David A. Hartmann, Kun Xie, Prakash Kara, Andy Y. Shih
bioRxiv 2021.01.29.428609; doi: https://doi.org/10.1101/2021.01.29.428609
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Precise, 3-D optogenetic control of the diameter of single arterioles
Philip J. O’Herron, David A. Hartmann, Kun Xie, Prakash Kara, Andy Y. Shih
bioRxiv 2021.01.29.428609; doi: https://doi.org/10.1101/2021.01.29.428609

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