Optogenetic control of arterial diameter in three-dimensions in vivo

Philip J. O’Herron, David A. Hartmann, Kun Xie, Prakash Kara, Andy Y. Shih

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

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 3-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. Wide-field photoactivation with an LED constricted all arteries in the imaging field leading to widespread reductions in blood flow. 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. We also demonstrate the confound in fluorescence imaging caused by changes in vessel diameter and discuss potential remedies.

Original languageEnglish (US)
Title of host publicationOptogenetics and Optical Manipulation 2024
EditorsAnna W. Roe, Shy Shoham
PublisherSPIE
ISBN (Electronic)9781510669178
DOIs
StatePublished - 2024
EventOptogenetics and Optical Manipulation 2024 - San Francisco, United States
Duration: Jan 27 2024 → …

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume12829
ISSN (Print)1605-7422

Conference

ConferenceOptogenetics and Optical Manipulation 2024
Country/TerritoryUnited States
CitySan Francisco
Period1/27/24 → …

Bibliographical note

Publisher Copyright:
© 2024 SPIE.

Keywords

  • neuroscience
  • neurovascular coupling
  • optical imaging
  • Optogenetics
  • ReaChR
  • Spatial Light Modulator
  • vascular dynamics

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