Developmental remodeling of the Drosophila nociceptive circuit

• Applicant: Dr. Sebastian Rumpf
• Subject Area: Developmental Neurobiology ; Sensory and Behavioural Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 552653341

Pruning, the regulated degeneration of neurites and synapses during development, is a widely used mechanism that serves to refine neuronal circuitry or to remove developmental intermediates. Pruning defects have also been linked to neurological diseases. The peripheral nociceptive class IV dendritic arborization (c4da) neurons of Drosophila larvae prune their dendrites at the onset of metamorphosis and then regenerate them for function in the adult. While the cell biological mechanisms of dendrite pruning are increasingly well understood, it is still unclear why they are remodeled. The identity of the nociceptive circuit downstream of c4da neurons is well established. It consists of a network of c4da neuron postsynaptic partners that compute appropriate reflexes depending on the noxious stimulus. Importantly, some of these stimuli - such as stings from parastitic wasps - are likely irrelevant for adult flies. Furthermore, recent evidence shows that c4da neurons not only prune their dendrites but also their presynaptic terminals, indicating that the nociceptive circuit also undergoes remodeling. We propose to study nociceptive circuit remodeling at several levels. At the cellular level, we will identify pruning pathways important for synapse pruning in c4da neurons. At the circuit level, we will follow the fate of the interneurons in the c4da neuron postsynaptic circuit during metamorphosis and adulthood. Furthermore, we will use available circuit-tracing tools to identify new postsynaptic partners of adult c4da neurons. At the animal level, we will identify the sensory modalities and behaviors mediated by adult c4da neurons. Diseases linked to pruning, such as autism spectrum disorders and schizophrenia, sometimes cause sensory paresthesia, highlighting a sensory component. As specific behavioral assays for c4da neurons have been established and their connectivity is known at the single neuron level, this system offers the opportunity to study remodeling and its behavioral consequences with high resolution. Taken together, our project will yield far-reaching insights into the development of neuronal connectivity.

• DFG Programme: Research Grants