Spreading depolarization in the brain of <i>Drosophila</i> is induced by inhibition of the Na<sup>+</sup>/K<sup>+</sup>-ATPase and mitigated by a decrease in activity of protein kinase G
Bibliographic record
Abstract
Spreading depolarization (SD) is characterized by a massive redistribution of ions accompanied by an arrest in electrical activity that slowly propagates through neural tissue. It has been implicated in numerous human pathologies, including migraine, stroke, and traumatic brain injury, and thus the elucidation of control mechanisms underlying the phenomenon could have many health benefits. Here, we demonstrate the occurrence of SD in the brain of Drosophila melanogaster, providing a model system, whereby cellular mechanisms can be dissected using molecular genetic approaches. Propagating waves of SD were reliably induced by disrupting the extracellular potassium concentration ([K(+)]o), either directly or by inhibition of the Na(+)/K(+)-ATPase with ouabain. The disturbance was monitored by recording the characteristic surges in [K(+)]o using K(+)-sensitive microelectrodes or by monitoring brain activity by measuring direct current potential. With the use of wild-type flies, we show that young adults are more resistant to SD compared with older adults, evidenced by shorter bouts of SD activity and attenuated [K(+)]o disturbances. Furthermore, we show that the susceptibility to SD differs between wild-type flies and w1118 mutants, demonstrating that our ouabain model is influenced by genetic strain. Lastly, flies with low levels of protein kinase G (PKG) had increased latencies to onset of both ouabain-induced SD and anoxic depolarization compared with flies with higher levels. Our findings implicate the PKG pathway as a modulator of SD in the fly brain, and given the conserved nature of the signaling pathway, it could likely play a similar role during SD in the mammalian central nervous system.
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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 | 0.001 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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".