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

Abstract

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 GABA A 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.