Kavli Affiliate: Michael Miller
| Authors: Niklas Krick, Jacob Davies, Bramwell Coulson, Daniel Sobrido-Camean, Michael Miller, Matthew C.W. Oswald, Aref Arzan Zarin, Richard Baines and Matthias Landgraf
| Summary:
As developing neural circuits become functional, they undergo a phase of heightened plasticity that facilitates network tuning in response to intrinsic and/or extrinsic stimuli. These developmental windows are termed critical periods (CPs), because perturbations during, but not outside the CP, can lead to lasting and significant changes, such as the formation of sub-optimal or unstable networks. How separate, but connected elements, within a network might respond differently to a CP perturbation is not well understood. To study this, we used the locomotor network of the Drosophila larva as an experimental model, using heat stress as an ecologically relevant CP stimulus. We show that increasing ambient temperature elevates locomotor network activity. When applied during the embryonic CP, heat stress leads to the formation of a network that has suboptimal output; causing larvae to crawl more slowly and requiring longer to recover from electroshock-induced seizures, indicative of decreased network stability. Within the central nervous system, we find transient embryonic CP perturbation leads to increased synaptic drive from premotor interneurons to motoneurons, which in turn adopt reduced excitability. In contrast, the peripheral neuromuscular junction, maintains normal synaptic transmission, despite significant structural changes of synaptic terminal overgrowth and altered postsynaptic receptor field composition. Overall, our data demonstrate that connected elements within a network respond differentially to a CP perturbation. Our results suggest a sequence, or hierarchy, of network adjustment during developmental CPs, and present the larval locomotor network as a highly tractable experimental model system with which to study CP biology.