D1 Dopamine receptors modulate cone ON bipolar cell Nav channels to control daily rhythms in photopic vision
Bibliographic record
Abstract
In amphibians, voltage-gated sodium (Nav) channels in cone ON bipolar cells (ON-CBC) amplify cone signals in the dark and in mesopic background light. However, during light adaptation, dopamine, acting through D1 receptors (D1R), suppresses Nav channels and therefore act as a gain control mechanism. Curiously in rodents, Nav channel contributions to the ON-CBC-generated light-adapted electroretinogram (ERG) b-wave appear to exist even in fully light-adapted conditions. We sought to determine how rodent ON-CBC Nav channels are regulated by dopamine via D1R during light adaptation and during the circadian cycle. We first tested the sensitivity of Nav channels in mouse ON-CBCs to the modulation by dopamine via D1Rs. Although light-adaptation had little effect on Nav channel contributions to the b-wave, these channels were found to be modulated by D1Rs. We pharmacologically isolated the cone to ON-CBC circuit in fully light-adapted retinas to confirm these results. Retinal dopamine release following light adaptation has been previously shown to be increased in mice during circadian night. We first show that circadian fluctuations in ON-CBC function are suppressed in dark-adapted retinas, indicating that circadian fluctuations are a function of light adaptation. Secondly, we show that at night the mouse retina behaves similarly to those of frogs and salamanders with a gain control mechanism utilizing D1R modulation of Nav channels to suppress ON-CBC light responses in light-adapted conditions during circadian night. Taken together, these results suggest that circadian control of ON-CBC function contains an initial phase after approximately 18-30 h of dark adaptation, leading to substantial changes in b-wave amplitude after a relatively short time in free run which are dependent on D1R modulation of Nav channels.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".