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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.
Pubmed ID: 39704728
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
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View all literature mentionsDrosophila melanogaster with name w[1118] P{y[+t7.7] w[+mC]=10xUAS-IVS-myr::smGdP-HA}attP18 P{y[+t7.7] w[+mC]=13xLexAop2-IVS-myr::smGdP-V5}su(Hw)attP8; sna[Sco]/CyO; P{y[+t7.7] w[+mC]=R58E02-GAL4.DBD}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=10XUAS-IVS-mCD8::GFP}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{GD35}v928 from Flybase.
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View all literature mentionsDrosophila melanogaster with name y[1] w[*] P{y[+t7.7] w[+mC]=UAS-myrGFP.QUAS-mtdTomato-3xHA}su(Hw)attP8; P{y[+t7.7] w[+mC]=trans-Tango}attP40 from BDSC.
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View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS04251}attP2 from BDSC.
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View all literature mentionsDrosophila melanogaster with name y[1] w[67c23]; P{w[+m*]=mb247-GAL80.T}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mW.hs]=GawB}MD806/TM6B, Tb[1] from BDSC.
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View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=13XLexAop2-IVS-GCaMP6s-p10}su(Hw)attP5 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR58E02-lexA}attP40 from BDSC.
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View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR58E02-GAL4}attP2 from BDSC.
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