Acute effects of drugs on <i>C.elegans</i> movement reveal complex responses and plasticity
Bibliographic record
Abstract
Abstract Many drugs act very rapidly — they can turn on or off their targets within minutes in a whole animal. What are the acute effects of drug treatment and how does an animal respond to these? We developed a simple assay to measure the acute effects of drugs on C.elegans movement and examined the effects of a range of compounds including neuroactive drugs, toxins, environmental stresses and novel compounds on worm movement over a time period of 3 hours. We find that many treatments show complex acute responses — a phase of rapid paralysis is followed by one or more recovery phases. The recoveries are not the result of some generic stress response but are specific to the drug e.g. recovery from paralysis due to a neuroactive drug requires neurotransmitter pathways whereas recovery from a metabolic inhibitor requires metabolic changes. Finally, we also find that acute responses can vary greatly across development and that there is extensive and complex natural variation in acute responses. In summary, acute responses are sensitive probes of the ability of biological networks to respond to drug treatment and these responses can reveal the action of unexplored pathways. Author Summary Drugs are powerful tools that let us switch on or off key pathways in whole animals and watch the effects. Here we set up a simple assay to measure how drugs affect the movement of the simple nematode C.elegans — crucially, we look how those responses change over time. We find that worms have complex responses to many different drugs — they go through clear phases of paralysis and recovery. The recovery from the initial effect of any drug is not due to a generic stress response but is specific to the way each drug acts. We find for example that worms can recover from paralysis driven by one neurotransmitter pathway by activating a different neurotransmitter pathway or from paralysis caused by loss of one metabolic pathway by turning on a second one. These complex responses show how the basic genetic networks that are needed for normal behaviour and function can rewire and respond to the effect of many drugs. Importantly, the responses can vary in many ways — different aged worms or different individuals can have different responses and capturing how drug responses change over time is critical to dissect this complexity.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".