ABSTRACT 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.

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