Bidirectional communication between astrocytes and arterioles controls vasomotion
Bibliographic record
Abstract
Authors: Grant Gordon¹ ¹University of Calgary Abstract: The resting perfusion of blood to the brain is immense and essential for proper function yet we have little understanding of how the brain regulates its basal blood supply. Astrocyte-mediated neurovascular coupling has conventionally been examined in the context of transient neuronally-evoked calcium (Ca2+) events triggering phasic changes in arteriole diameter to control blood flow. However, our group recently demonstrated that "resting" astrocyte Ca2+ levels control tonic, neural activity independent, brain blood flow. It was unclear if or how fluctuations in resting astrocyte Ca2+ regulated vascular tone in vivo. Using two-photon fluorescence imaging, astrocyte patch-clamp, pharmacology, chemogenetics and cre-lox gene knockdown in acute cortical brain slices and in vivo, we showed that increases in arteriole tone (vasoconstriction) caused a sustained elevation in the astrocyte endfoot Ca2+ level. Pharmacology suggested that a TRPV4-mediated Ca2+ influx initiated a Ca2+-dependent COX-1 pathway in endfeet that triggered the release of prostaglandin vasodilators. The role of endfoot COX-1 was further demonstrated with astrocyte specific cre-lox knockdown of the COX-1 gene PTGS1. Furthermore, chemogenetic control of arteriole constriction was sufficient to engage this pathway. While in brain slices this pathway appeared to be a static effect on arteriole tone, in awake mice in vivo, we found this pathway was involved in vasomotion - a pulsatile phenomenon of vascular contraction and relaxation occurring at ~0.1Hz which is important for the basal perfusion of tissue. Using an astrocyte selective AAV to overexpress a Ca2+ extrusion pump called CalEx, which clamps astrocyte free Ca2+ at a lower level and prevents increases, this largely abolished vasomotion compared to control virus. Our data demonstrated that bidirectional communication between astrocyte endfeet and arterioles is important for setting basal arteriole tone and vasomotion in vivo, which is likely an essential process for optimizing cerebral perfusion of oxygenated blood.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".