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Peer-reviewedCC BY 4.0Genetics

Neuroligin 3 highlights the sexually dimorphic neural substrates of Drosophila social spacing

  • J Wesley Robinson
  • Abigail T Bechard
  • Micah R Evans
  • Judy Kurbaj
  • Reza Ataei
  • Khadijat O Mosuro
  • Sanjali Pillay
  • Daisy S Lin
  • Avneet Sahota
  • Jade N de Belle
  • Gregory I Robinson
  • Ryley T Yost
2 more authors
  • Amanda J Moehring
  • Anne F Simon
Read full textPDFDOICite

Abstract

In Drosophila melanogaster, Neuroligin 3 (Nlg3) is a postsynaptic membrane protein important for synapse development and social spacing behavior, and its human orthologs are associated with autism. We localized Nlg3 to 3 brain structures: the mushroom bodies (MB) calyx, the optic lobes (OL), and the protocerebral bridge (PB). RNA knockdown of nlg3 in each structure independently replicated the effect of knocking down in all nlg3-expressing neurons. In contrast, hyperactivating and silencing all nlg3-expressing neurons, including those within the MB, PB, and OL, affected social spacing by sex: females were further apart after either manipulation, whereas males’ social space was increased, only after hyperactivation. Decreasing acetylcholine release in the MB via choline acetyltransferase (ChAT)-RNAi caused decreased social space in both sexes. In contrast, RNAi targeting dopamine receptors in the MB increased social space mainly in males. Finally, we also tested fruitless-expressing (fruP1) neurons, which regulate sexually dimorphic behaviors. Hyperactivating fruP1 neurons decreased social space in both sexes, while silencing increased social space only in males. These results highlight sex-specific neural substrates for social space and implicate the OL, MB, nlg3, and fruP1 neurons, in this behavior.

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Cite

BibTeXRIS
BibTeX
@article{robinson2026neuroligin,
  title = {{Neuroligin 3 highlights the sexually dimorphic neural substrates of Drosophila social spacing}},
  author = {J Wesley Robinson and Abigail T Bechard and Micah R Evans and Judy Kurbaj and Reza Ataei and Khadijat O Mosuro and Sanjali Pillay and Daisy S Lin and Avneet Sahota and Jade N de Belle and Gregory I Robinson and Ryley T Yost and Amanda J Moehring and Anne F Simon},
  journal = {Genetics},
  year = {2026},
  month = sep,
  doi = {10.1093/genetics/iyag243},
  url = {https://doi.org/10.1093/genetics/iyag243},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Neuroligin 3 highlights the sexually dimorphic neural substrates of Drosophila social spacing
AU  - J Wesley Robinson
AU  - Abigail T Bechard
AU  - Micah R Evans
AU  - Judy Kurbaj
AU  - Reza Ataei
AU  - Khadijat O Mosuro
AU  - Sanjali Pillay
AU  - Daisy S Lin
AU  - Avneet Sahota
AU  - Jade N de Belle
AU  - Gregory I Robinson
AU  - Ryley T Yost
AU  - Amanda J Moehring
AU  - Anne F Simon
PY  - 2026
DA  - 2026/09/08
JO  - Genetics
DO  - 10.1093/genetics/iyag243
UR  - https://doi.org/10.1093/genetics/iyag243
AB  - In Drosophila melanogaster, Neuroligin 3 (Nlg3) is a postsynaptic membrane protein important for synapse development and social spacing behavior, and its human orthologs are associated with autism. We localized Nlg3 to 3 brain structures: the mushroom bodies (MB) calyx, the optic lobes (OL), and the protocerebral bridge (PB). RNA knockdown of nlg3 in each structure independently replicated the effect of knocking down in all nlg3-expressing neurons. In contrast, hyperactivating and silencing all nlg3-expressing neurons, including those within the MB, PB, and OL, affected social spacing by sex: females were further apart after either manipulation, whereas males’ social space was increased, only after hyperactivation. Decreasing acetylcholine release in the MB via choline acetyltransferase (ChAT)-RNAi caused decreased social space in both sexes. In contrast, RNAi targeting dopamine receptors in the MB increased social space mainly in males. Finally, we also tested fruitless-expressing (fruP1) neurons, which regulate sexually dimorphic behaviors. Hyperactivating fruP1 neurons decreased social space in both sexes, while silencing increased social space only in males. These results highlight sex-specific neural substrates for social space and implicate the OL, MB, nlg3, and fruP1 neurons, in this behavior.
SN  - 0016-6731
SN  - 1943-2631
ER  -