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Record W4414904860 · doi:10.1101/2025.10.06.680750

Neuromodulation of zebrafish primary motoneuron firing is shaped by developmental changes in the M-current

2025· preprint· en· W4414904860 on OpenAlexafffund
Stephanie F. Gaudreau, Tuan V. Bui

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicTranscranial Magnetic Stimulation Studies
Canadian institutionsUniversity of Ottawa
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsNeuromodulationAcetylcholineZebrafishSerotonin5-HT receptorNeurotransmitterInhibitory postsynaptic potentialBiological neural networkAcetylcholine receptorInterneuron

Abstract

fetched live from OpenAlex

ABSTRACT Movements during development are refined through the ongoing maturation of the spinal circuits that mediate them. In many vertebrates, including zebrafish, this maturation process involves neuromodulators such as acetylcholine, serotonin, and dopamine; however, the targets of this neuromodulation remain largely unknown. Recent work has revealed distinct developmental dynamics of the non-inactivating subthreshold potassium current – the M-current – in primary motoneurons of larval zebrafish. Considering that neuromodulators play a role in the maturation of locomotor control in larval zebrafish, we asked whether neuromodulators might target the M-current in primary motoneurons during development. Our patch-clamp experiments in primary motoneurons of zebrafish aged 3 to 5 days post-fertilization (dpf) reveal distinct modulation of the M-current by serotonin and acetylcholine that is age-dependent. Our data demonstrates an inhibitory influence of serotonin signaling via 5HT 1A receptors that promotes repetitive firing in primary motoneurons specifically at 3 dpf. We also show that acetylcholine, likely via M2/M4 receptors, enhances the M-current and limits repetitive firing in primary motoneurons but does so only after 3 dpf. Modulation of the M-current in primary motoneurons was not observed across all neuromodulators as dopamine had no effect at any age. Considering that the M-current transiently peaks at 3 dpf and is reduced at 4 and 5 dpf, our findings suggest that the developmental changes in this current can shape how neuromodulators modulate firing properties of primary motoneurons. Key points The amplitude of the M-current is subject to modulation by several neuromodulators such as acetylcholine and serotonin Serotonin via 5HT 1A inhibits the M-current in primary motoneurons at 3 dpf Muscarinic agonist enhances the M-current in primary motoneurons after 3 dpf Neuromodulation of motoneuron firing properties by 5-HT 1A and muscarinic agonist is consistent with modulation of the M-current

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.032
GPT teacher head0.248
Teacher spread0.216 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

Explore more

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