Phosphorylation of Gephyrin in Zebrafish Mauthner Cells Governs Glycine Receptor Clustering and Behavioral Desensitization to Sound
Bibliographic record
Abstract
The process by which future behavioral responses are shaped by past experiences is one of the central questions in neuroscience. To gain insight into this process at the molecular and cellular levels, we have applied zebrafish larvae to explore behavioral desensitization to sound. A sudden loud noise often evokes a defensive response known as the acoustic startle response (ASR), which is triggered by firing Mauthner cells in teleosts and amphibians. The probability of evoking ASR by suprathreshold sound is reduced after exposure to repetitive auditory stimuli insufficient in amplitude to evoke the ASR (subthreshold). Although it has been suggested that the potentiation of inhibitory glycinergic inputs into Mauthner cell is involved in this desensitization of the ASR, the molecular basis for the potentiation of glycinergic transmission has been unclear. Through the in vivo monitoring of fluorescently-tagged glycine receptors (GlyRs), we here showed that behavioral desensitization to sound in zebrafish is governed by GlyR clustering in Mauthner cells. We further revealed that CaMKII-dependent phosphorylation of the scaffolding protein gephyrin at serine 325 promoted the synaptic accumulation of GlyR on Mauthner neurons through the enhancement of the gephyrin-GlyR binding, which was indispensable for and could induce desensitization of the ASR. Our study demonstrates an essential molecular and cellular basis of sound-induced receptor dynamics and thus of behavioral desensitization to sound. SIGNIFICANCE STATEMENT Behavioral desensitization in the acoustic startle response of fish is known to involve the potentiation of inhibitory glycinergic input to the Mauthner cell, which is a command neuron for the acoustic startle response. However, the molecular and cellular basis for this potentiation has been unknown. Here we show that an increase in glycine receptor (GlyR) clustering at synaptic sites on zebrafish Mauthner cells is indispensable for and could induce desensitization. Furthermore, we demonstrate that CaMKII-mediated phosphorylation of the scaffolding protein gephyrin promotes GlyR clustering by increasing the binding between the β-loop of GlyRs and gephyrin. Thus, the phosphorylation of gephyrin is a key event which accounts for the potentiation of inhibitory glycinergic inputs observed during sound-evoked behavioral desensitization.
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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".