@article{1c37e8d72b6b4b13833ae898d3233719,
title = "A Feedforward Circuit Regulates Action Selection of Pre-mating Courtship Behavior in Female Drosophila",
abstract = "In the early phase of courtship, female fruit flies exhibit an acute rejection response to avoid unfavorable mating. This pre-mating rejection response is evolutionarily paralleled across species, but the molecular and neuronal basis of that behavior is unclear. Here, we show that a putative incoherent feedforward circuit comprising ellipsoid body neurons, cholinergic R4d, and its repressor GABAergic R2/R4m neurons regulates the pre-mating rejection response in the virgin female Drosophila melanogaster. Both R4d and R2/R4m are positively regulated, via specific dopamine receptors, by a subset of neurons in the dopaminergic PPM3 cluster. Genetic deprivation of GABAergic signal via GABAA receptor RNA interference in this circuit induces a massive rejection response, whereas activation of GABAergic R2/R4m or suppression of cholinergic R4d increases receptivity. Moreover, glutamatergic signaling via N-methyl-D-aspartate receptors induces NO-mediated retrograde regulation potentially from R4d to R2/R4m, likely providing flexible control of the behavioral switching from rejection to acceptance. Our study elucidates the molecular and neural mechanisms regulating the behavioral selection process of the pre-mating female. Ishimoto and Kamikouchi report on a subclass of dopaminergic neurons that drive a feedforward circuit comprising cholinergic and GABAergic neurons that regulates the pre-mating behavior of virgin females in Drosophila. A glutamate/NMDAR and NO retrograde signal modulates the circuit function to abolish the rejection response toward the males{\textquoteright} attempts to copulate.",
keywords = "Drosophila, central complex, courtship, dopamine, ellipsoid body, feedforward, receptivity, sexual motivation",
author = "Hiroshi Ishimoto and Azusa Kamikouchi",
note = "Funding Information: We thank T. Kitamoto, K. Kume, M. Gallio, the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center, the Kyoto Stock Center, and FlyLight for the fly stocks. We also thank T. Kitamoto, K. Kimura, T. Awasaki, H. Shiozaki, Y. Ishikawa, R. Tanaka, and X. Li for comments and discussion and M. Kuno, Y. Maki, and Y. Ishikawa for fly maintenance. This work was supported by MEXT KAKENHI Grants-in-Aid for Scientific Research (B) (grant JP16H04655 to A.K.), Scientific Research on Innovative Areas “Evolinguistics” (grant JP18H05069 to A.K.), Systems Science of Bio-navigation (grant 19H04933 to A.K.), Challenging Research (Exploratory) (grant 17K19450 to A.K.), Grant-in Aid for Scientific Research (C) ( 15K07147 and 18K06332 to H.I.), the Naito Foundation (to A.K.), and the Inamori Foundation Research Grant, Japan (to H.I.). Funding Information: We thank T. Kitamoto, K. Kume, M. Gallio, the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center, the Kyoto Stock Center, and FlyLight for the fly stocks. We also thank T. Kitamoto, K. Kimura, T. Awasaki, H. Shiozaki, Y. Ishikawa, R. Tanaka, and X. Li for comments and discussion and M. Kuno, Y. Maki, and Y. Ishikawa for fly maintenance. This work was supported by MEXT KAKENHI Grants-in-Aid for Scientific Research (B) (grant JP16H04655 to A.K.), Scientific Research on Innovative Areas ?Evolinguistics? (grant JP18H05069 to A.K.), Systems Science of Bio-navigation (grant 19H04933 to A.K.), Challenging Research (Exploratory) (grant 17K19450 to A.K.), Grant-in Aid for Scientific Research (C) (15K07147 and 18K06332 to H.I.), the Naito Foundation (to A.K.), and the Inamori Foundation Research Grant, Japan (to H.I.). H.I. and A.K. conceived and designed the experiments. H.I. carried out the experiments and analyzed the data. H.I. and A.K. wrote the paper. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2020",
month = feb,
day = "3",
doi = "10.1016/j.cub.2019.11.065",
language = "English",
volume = "30",
pages = "396--407.e4",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "3",
}