Astrocytic Gq-GPCR-Linked IP3R-Dependent Ca2+ Signaling Does Not Mediate Neurovascular Coupling in Mouse Visual Cortex in vivo Public Deposited

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  • March 19, 2019
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  • Bonder, Daniel
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum, Neuroscience Center
Abstract
  • Local blood flow is modulated in response to changing patterns of neuronal activity (Roy and Sherrington, 1890), a process termed neurovascular coupling. It has been proposed that the central cellular pathway driving this process is astrocytic Gq-GPCR-linked IP3R-dependent Ca2+ signaling, though in vivo tests of this hypothesis are largely lacking. We examined the impact of astrocytic Gq-GPCR and IP3R-dependent Ca2+ signaling on cortical blood flow in awake, responsive mice using multiphoton laser-scanning microscopy and novel genetic tools that enable the selective manipulation of astrocytic signaling pathways in vivo. Selective stimulation of astrocytic Gq-GPCR cascades and downstream Ca2+ signaling with the hM3Dq DREADD designer receptor system was insufficient to modulate basal cortical blood flow. We found no evidence of observable astrocyte endfeet Ca2+ elevations following physiological visual stimulation despite robust dilations of adjacent arterioles using cyto-GCaMP3 and Lck-GCaMP6s, the most sensitive Ca2+ indicator available. Astrocytic Ca2+ elevations could be evoked when inducing the startle response with unexpected air puffs. However, startle-induced astrocytic Ca2+ signals did not precede corresponding startle-induced hemodynamic changes. Further, neurovascular coupling was intact in awake, responsive mice genetically lacking astrocytic IP3R-dependent Ca2+ signaling (IP3R2 KO). These data establish that astrocytic Gq-GPCR-linked IP3R-dependent Ca2+ signaling does not mediate neurovascular coupling in visual cortex of awake, responsive mice.
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  • In Copyright
Advisor
  • Smith, Spencer
  • McCarthy, Ken D.
  • Deshmukh, Mohanish
  • Kash, Thomas
  • Philpot, Benjamin
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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