Increases in respiration can increase brain oxygenation without flow changes. Neurovascular coupling is irregular, absent, or inverted in many brain regions, behavioral states, and conditions. Baseline blood flow is adequate to supply oxygen needs even with elevated neural activity. However, there is a large body of evidence that is inconsistent with this idea. The common explanation for increased blood flow (known as functional hyperemia) is that it supplies the metabolic needs of active neurons. In the brain, increases in neural activity drive changes in local blood flow via neurovascular coupling. All summary data are presented as mean ± SEM. The inset scatterplots (bottom right) show correlation coefficients between diameter and Ca 2+ for all data points at zero time lag. (K and L) Cross-correlation of diameter versus endfoot Ca 2+ changes for control (K, red) and CalEx (L, blue). Right panels show summary data at 0.1 Hz frequency (unpaired t test). (J) Frequency power analysis of arteriole diameter fluctuations (top control in red, CalEx in blue) and endfoot Ca 2+ fluctuations (bottom control in orange, CalEx in purple). (I) Peak-to-trough Ca 2+ measurements in Tdtomato control animals (orange) versus CalEx (purple)(unpaired t test).
CALEX NETWORK INTERFACE SERIES
(H) Summary time series of Ca 2+ traces aligned via cross-correlation showing diameter fluctuations in Tdtomato control animals (orange) versus CalEx (purple). (G) Representative endfoot Ca 2+ traces showing Ca 2+ fluctuations in Tdtomato control animals (orange) that are disrupted in CalEx (purple). (F) Peak-to-trough diameter measurements in control animals (red) versus CalEx (blue) (unpaired t test).
(E) Summary time series of diameter traces aligned via cross-correlation showing diameter fluctuations in Tdtomato control animals (red) versus CalEx (blue). (D) Representative arteriole diameter traces showing vasomotor fluctuations in Tdtomato control animals (n = 12 arterioles, n = 12 animals) (red) that are disrupted in CalEx (n = 16 arterioles, n = 16 animals) (blue). (C) Post hoc immunofluorescence images showing astrocyte GCaMP6f fluorescence (cyan) and the mCherry reporter used to visualize the CalEx construct (magenta). (C) Representative image of penetrating arteriole lumen visualized via rhodamine-dextran (magenta) and astrocyte-specific GCaMP6f fluorescence (cyan). (B) Representative image of the cranial window showing astrocyte-specific GCaMP6f fluorescence (cyan).
Clamping astrocyte Ca 2+ in vivo with CalEx impairs vasomotion (A) Cartoons depicting the awake-mouse, in vivo setup whereby a trained, head-restrained animal is on a passive, air-supported Styrofoam ball (top) during imaging through a cranial window (bottom).
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