Voltage‐gated sodium channel‐dependent retroaxonal modulation of photoreceptor function during post‐natal development in mice
Bibliographic record
Abstract
Abstract Juvenile (postnatal day 16) mice lacking Nav1.6 channels (null‐mutant Scn8admu) have reduced photoreceptor function, which is unexpected given that Nav channels have not been detected in mouse photoreceptors and do not contribute appreciably to photoreceptor function in adults. We demonstrate that acute block of Nav channels with intravitreal TTX in juvenile (P16) wild‐type mice has no effect on photoreceptor function. However, reduced light activity by prolonged dark adaptation from P8 caused significant reduction in photoreceptor function at P16. Injecting TTX into the retrobulbar space at P16 to specifically block Nav channels in the optic nerve also caused a reduction in photoreceptor function comparable to that seen at P16 in null‐mutant Scn8a mice. In both P16 null‐mutant Scn8admu and retrobulbar TTX‐injected wild‐type mice, photoreceptor function was restored following intravitreal injection of the TrkB receptor agonist 7,8‐dihydroxyflavone, linking Nav‐dependent retrograde transport to TrkB‐dependent neurotrophic factor production pathways as a modulatory influence of photoreceptor function at P16. We also found that in Scn8admu mice, photoreceptor function recovers by P22‐25 despite more precarious general health of the animal. Retrobulbar injection of TTX in the wild type still reduced the photoreceptor response at this age but to a lesser extent, suggesting that Nav‐dependent modulation of photoreceptor function is largely transient, peaking soon after eye opening. Together, these results suggest that the general photosensitivity of the retina is modulated following eye opening by retrograde transport through activity‐dependent retinal ganglion cell axonal signaling targeting TrkB receptors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".