Chemogenetic ablation of dopaminergic neurons leads to transient locomotor impairments in zebrafish larvae
Bibliographic record
Abstract
Abstract To determine the impact of a controlled loss of dopaminergic neurons on locomotor function, we generated transgenic zebrafish, Tg( dat : CFP ‐ NTR ), expressing a cyan fluorescent protein‐nitroreductase fusion protein ( CFP ‐ NTR ) under the control of dopamine transporter ( dat ) cis ‐regulatory elements. Embryonic and larval zebrafish express the transgene in several groups of dopaminergic neurons, notably in the olfactory bulb, telencephalon, diencephalon and caudal hypothalamus. Administration of the pro‐drug metronidazole (Mtz) resulted in activation of caspase 3 in CFP ‐positive neurons and in a reduction in dat ‐positive cells by 5 days post‐fertilization (dpf). Loss of neurons coincided with impairments in global locomotor parameters such as swimming distance, percentage of time spent moving, as well as changes in tail bend parameters such as time to maximal bend and angular velocity. Dopamine levels were transiently decreased following Mtz administration. Recovery of some of the locomotor parameters was observed by 7 dpf. However, the total numbers of dat ‐expressing neurons were still decreased at 7, 12, or 14 dpf, even though there was evidence for production of new dat ‐expressing cells. Tg( dat : CFP ‐ NTR ) zebrafish provide a model to correlate altered dopaminergic neuron numbers with locomotor function and to investigate factors influencing regeneration of dopaminergic neurons. image We have generated transgenic zebrafish expressing nitroreductase for the conditional and specific ablation of dopaminergic (DA) neurons in the larval zebrafish brain. We are able to induce a persistent reduction in DA neurons with transient locomotor impairments. Our transgenic zebrafish offer a model for understanding the impact of altered DA neuron populations on larval locomotor function and for the study of dopamine neuron regeneration following tissue specific ablation.
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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 | 0.001 |
| 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".