A neurotrophin functioning with a Toll regulates structural plasticity in a dopaminergic circuit

Sun, Jun; Rojo-Cortés, Francisca; Ulian-Benitez, Suzana; Forero, Manuel G; Li, Guiyi; Singh, Deepanshu; Wang, Xiaocui; Cachero, Sebastian; Moreira, Marta; Kavanagh, Dean; Jefferis, Gregory; Croset, Vincent; Hidalgo, Alicia

Abstract

Experience shapes the brain, as neural circuits can be modified by neural stimulation or the lack of it. The molecular mechanisms underlying structural circuit plasticity and how plasticity modifies behaviour, are poorly understood. Subjective experience requires dopamine, a neuromodulator that assigns a value to stimuli, and it also controls behaviour, including locomotion, learning and memory. In Drosophila, Toll receptors are ideally placed to translate experience into structural brain change. Toll-6 is expressed in dopaminergic neurons (DANs), raising the intriguing possibility that Toll-6 could regulate structural plasticity in dopaminergic circuits. Drosophila neurotrophin-2 (DNT-2) is the ligand for Toll-6, but whether it is required for circuit structural plasticity was unknown. Here, we show that DNT-2 expressing neurons connect with DANs, and they modulate each other. Loss of function for DNT-2 or its receptors Toll-6 and kinase-less Trk-like kek-6 caused DAN and synapse loss, impaired dendrite growth and connectivity, decreased synaptic sites and caused locomotion deficits. By contrast, over-expressed DNT-2 increased dendrite complexity and promoted synaptogenesis. Neuronal activity increased synaptogenesis in DNT-2 and DANs, and over-expression of DNT-2 could mimic this effect. Altering the levels of DNT-2 or Toll-6 could also modify 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 brain function.

Citation

Sun, J., Rojo-Cortés, F., Ulian-Benitez, S., Forero, M. G., Li, G., Singh, D., Wang, X., Cachero, S., Moreira, M., Kavanagh, D., Jefferis, G., Croset, V., & Hidalgo, A. (2024). A neurotrophin functioning with a Toll regulates structural plasticity in a dopaminergic circuit. eLife, 13, Article RP102222. https://doi.org/10.7554/elife.102222.1

• Journal Article Type: Article
• Acceptance Date: Oct 10, 2024
• Online Publication Date: Oct 24, 2024
• Publication Date: Oct 24, 2024
• Deposit Date: Oct 31, 2024
• Journal: eLife
• Electronic ISSN: 2050-084X
• Publisher: eLife Sciences Publications
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Article Number: RP102222
• DOI: https://doi.org/10.7554/elife.102222.1
• Public URL: https://durham-repository.worktribe.com/output/2994255