Structural circuit plasticity by a neurotrophin with a Toll modifies dopamine-dependent behaviour

• Published in: bioRxiv
• Main Authors: Sun, Jun, Ulian-Benitez, Suzana, ero, Manuel G, Li, Guiyi, Singh, Deepanshu, Cachero, Sebastian, Rojo-Cortes, Francisca R, Moreira, Marta, Kavanagh, Dean, Gregory S X E Jefferis, Hidalgo, Alicia
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.01.2023
• Subjects: Arousal; Axon guidance; Dopamine; Dopamine receptors; Drosophila; Insects; Locomotion; Long term memory; Motivation; Neural plasticity; Neuromodulation; Neurons; Neurotrophin 2; Synaptogenesis
• DOI: 10.1101/2023.01.04.522695

Toll receptors are expressed in the distinct anatomical brain modules and can regulate structural brain plasticity in adult Drosophila. Structural plasticity in response to neuronal activity and experience could enable adaptation, and its deficit could underlie brain dysfunction and disease. Thus, a key goal is to understand how structural circuit changes modify behaviour. Subjective experience requires dopamine, a neuromodulator that controls arousal, motivation and locomotion, and assigns a value to stimuli. Toll-6 is expressed in dopaminergic neurons (DANs), raising the intriguing possibility that Toll-6 could regulate plasticity in dopaminergic circuits. Drosophila neurotrophin-2 (DNT-2) is the ligand for Toll-6, but it is unknown whether it is required for structural circuit plasticity. Here, we show that structural plasticity depends on the activity-dependent increase and activation of DNT-2, which in turn functions via its Toll-6 and kinase-less Trk-like Kek-6 receptors in DANs, modifying behaviour. DNT-2 expressing neurons are anatomically and functionally connected with DANs, and they modulate each other. Loss of DNT-2 or Toll-6 and kek-6 function caused DAN loss and synapse loss, and alterations in their levels compromised dendritic size and complexity and axonal targeting of analysed single neurons. Neuronal activity-dependent synapse formation required DNT-2, Toll-6 and Kek-6. Furthermore, structural plasticity in an associative, dopaminergic circuit modified dopamine-dependent behaviours, including locomotion and long-term memory. We conclude that an activity-dependent feedback loop involving dopamine and DNT-2 labelled the circuits engaged, and DNT-2 with Toll-6 and Kek-6 induced structural plasticity in this circuit, modifying behaviour.Competing Interest StatementThe authors have declared no competing interest.