Dual cholinergic and serotonergic excitatory pathways mediate oxygen sensing in the zebrafish gill
Bibliographic record
Abstract
Abstract The evolution of oxygen sensing included a transition from a diffuse distribution of respiratory chemoreceptors in the gills of water‐breathing vertebrates to chemoreceptor clusters confined to the pulmonary epithelium and carotid body in air‐breathers. Since the excitatory neurotransmitters mediating oxygen sensing in anamniotes have never been confirmed, the origins of oxygen sensing in vertebrates have remained controversial. In gills isolated from Tg( elavl3 :GCaMP6s) zebrafish expressing a genetically encoded reporter of intracellular Ca 2+ concentration ([Ca 2+ ] i ), we demonstrate that acetylcholine (ACh) and nicotine induced a dose‐dependent increase in [Ca 2+ ] i in postsynaptic sensory neurons innervating oxygen‐chemoreceptive neuroepithelial cells (NECs). Hypoxic stimulation of NECs evoked a similar rise in neuronal [Ca 2+ ] i that was abolished by the nicotinic antagonist hexamethonium. Using immunohistochemistry and RT‐qPCR, we identified a novel population of ACh‐containing NECs associated with sensory neurons expressing the α2 subunit of nicotinic ACh receptors. In vivo whole‐larva Ca 2+ imaging showed that cholinergic and hypoxic activation of the gills generated Ca 2+ activity in neurons of vagal sensory ganglia with time‐dependent characteristics of neurotransmission towards the hindbrain. We identified a second source of hypoxic activity in vagal sensory ganglia operating exclusively through 5‐HT 3 receptors and dependent upon vesicular monoamine transport (VMAT2) in the gill. We traced expression of 5‐HT 3 receptors to nerve terminals surrounding a separate population of serotonergic VMAT2‐positive NECs. Our investigation reveals independent cholinergic and serotonergic autonomic pathways of oxygen sensing in zebrafish and provides novel physiological evidence consistent with the idea that gill chemoreceptors are homologues of both pulmonary and carotid body chemoreceptors in mammals. image Key points The excitatory neurotransmitters mediating oxygen sensing in anamniotes have never been confirmed. Thus, the origins of oxygen sensing in vertebrates have remained controversial. In transgenic zebrafish expressing a genetically encoded reporter of intracellular Ca 2+ concentration, we identified two independent pathways of oxygen sensing in the gill: one involving acetylcholine and interneurons intrinsic to the gill, and the other via serotonin acting directly upon ganglionic neurons. Both pathways resulted in excitation of vagal sensory ganglia that receive hypoxic inputs from the gills and innervate the hindbrain. We argue that gill chemoreceptors are homologues of both pulmonary and carotid body chemoreceptors in mammals.
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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 | 0.000 | 0.000 |
| 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".