# Maturation of GABAergic signalling times the opening of a critical period in Drosophila melanogaster

**Authors:** Jack Corke, Mariam Huertas-Radi, Matthias Landgraf, Richard A. Baines

PMC · DOI: 10.1038/s41598-025-24116-2 · Scientific Reports · 2025-11-17

## TL;DR

This study shows that GABAergic signaling controls the timing of a critical period in the development of the fruit fly's nervous system, similar to what happens in mammals.

## Contribution

The study demonstrates that GABAergic signaling regulates the timing of a critical period in Drosophila, suggesting a conserved mechanism across species.

## Key findings

- Enhancing GABAergic signaling with diazepam or overexpression of rdl caused early opening of the critical period.
- Blocking GABAergic signaling with gabazine or Gad1 knockdown delayed the critical period's opening.
- GABAergic signaling dictates the timing of the critical period in Drosophila's CNS.

## Abstract

Critical periods (CPs) during the development of neural networks are widely documented. Activity manipulation during open CPs leads to debilitating effects to the mature neural network. Detailed understanding of the contribution of CPs to network development, however, remains elusive. This is partly because mammalian CPs are present in complex sensory networks (e.g., visual), making focused experimental manipulation challenging. It is significant, therefore, that CPs have been identified in simpler models. An embryonic CP occurs during locomotor network development in Drosophila melanogaster. Perturbation of neuronal activity during this period destabilises the larval locomotor network: rendering it seizure prone. Given the role of GABA in the timing of the mammalian CP of ocular dominance, we investigated whether a similar role exists for the Drosophila CP. Utilising GABA pharmacology and genetics, we manipulated the embryonic GABAergic system and measured an induced seizure phenotype in third-instar larvae. Potentiating GABAergic signalling, via exposure to diazepam (agonist) or overexpression of the GABAA receptor rdl, induced precocious opening of the CP. By contrast, exposure to gabazine (antagonist), or knockdown of the GABA-synthetic enzyme Gad1, delayed opening. Thus, we show that CP timing within the Drosophila CNS is dictated by GABAergic signalling, indicating a phylogenetically conserved role.

## Linked entities

- **Genes:** LEO1 (LEO1 component of Paf1/RNA polymerase II complex) [NCBI Gene 123169], GAD1 (glutamate decarboxylase 1) [NCBI Gene 2571]
- **Chemicals:** diazepam (PubChem CID 3016), gabazine (PubChem CID 107895)
- **Species:** Drosophila melanogaster (taxon 7227)

## Full-text entities

- **Genes:** Rdl (Resistant to dieldrin) [NCBI Gene 39054] {aka CG10537, CT29555, DGABAAR, DmRDL, DmRdl, Dmel\CG10537}
- **Diseases:** seizure (MESH:D012640), CP (MESH:D002972)
- **Chemicals:** diazepam (MESH:D003975), gabazine (MESH:C049853), GABAergic (-), GABA (MESH:D005680)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12623761/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12623761/full.md

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Source: https://tomesphere.com/paper/PMC12623761