The role of a critical period in the development of the Drosophila locomotor network

Abstract

Although a substantial amount is known about individual neurons, the early developmental rules that orchestrate the formation of neural circuits and how these may differ over time remain comparatively less understood. This includes identifiable critical periods of development, in which windows of maximal plasticity appear crucial for circuit-level refinement. Research has predominantly aimed to explicate these processes using mammalian models with large complex central nervous systems. Due to the scale and complexity, these models are more limited for characterising how cellular dynamics alter global network function. Model organisms such as Drosophila Melanogaster present viable options to better examine these processes due the comparative numerical simplicity of total neurons, whilst also retaining a high degree of complexity. Much of the larval brain has been characterised, which permits both manipulation and investigation at the resolution of individual neurons, providing insight into how activity during critical periods (CPs) shape neural network development. By utilising a model circuit (aCC motoneurons), we provide evidence of alterations in the excitation : inhibition (E:I) balance after critical period manipulation. We also demonstrate that increased mechanosensory input can have diverse repercussions at both the behavioural and neuronal level. Excitation of chordotonal neurons confined to the larval CP was found to be capable of rescuing the increased seizure phenotype normally present in the genetic seizure mutant bss. whereas this same perturbation is capable of inducing a seizure phenotype in wild type larvae. Finally, we present preliminary evidence that homeostatic set points are established during the CP, with optogenetic excitation and inhibition of the premotor interneuron A27h during the critical period resulting in A27h exhibiting increased or decreased intrinsic excitability respectively in L3 larva.

Date of Award	1 Aug 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Rasmus Petersen (Supervisor) & Richard Baines (Supervisor)