| Title: |
A neurotrophin functioning with a Toll regulates structural plasticity in a dopaminergic circuit |
| Authors: |
Sun, Jun; Rojo-Cortes, Francisca; Ulian-Benitez, Suzana; Forero, Manuel G; Li, Guiyi; Singh, Deepanshu ND; Wang, Xiaocui; Cachero, Sebastian; Moreira, Marta; Kavanagh, Dean; Jefferis, Gregory SXE; Croset, Vincent; Hidalgo, Alicia |
| Contributors: |
HORIZON EUROPE Marie Sklodowska-Curie Actions; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Wellcome Trust; Darwin Trust of Edinburgh; Biotechnology and Biological Sciences Research Council |
| Source: |
eLife ; volume 13 ; ISSN 2050-084X |
| Publisher Information: |
eLife Sciences Publications, Ltd |
| Publication Year: |
2024 |
| Collection: |
eLife (E-Journal - via CrossRef) |
| Description: |
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 and Kek-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. In contrast, over-expressed DNT-2 increased DAN cell number, dendrite complexity, and promoted synaptogenesis. Neuronal activity modified DNT-2, increased synaptogenesis in DNT-2-positive neurons and DANs, and over-expression of DNT-2 did too. Altering the levels of DNT-2 or Toll-6 also modified dopamine-dependent behaviours, including locomotion and long-term memory. To conclude, a feedback loop involving dopamine and DNT-2 highlighted the circuits engaged, and DNT-2 with Toll-6 and Kek-6 induced structural plasticity in this circuit modifying brain function and behaviour. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.7554/elife.102222.3 |
| Availability: |
https://doi.org/10.7554/elife.102222.3; https://cdn.elifesciences.org/articles/102222/elife-102222-v1.pdf; https://cdn.elifesciences.org/articles/102222/elife-102222-v1.xml; https://elifesciences.org/articles/102222 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.E98FFA4 |
| Database: |
BASE |