A Feedforward Circuit Regulates Action Selection of Pre-mating Courtship Behavior in Female Drosophila

Hiroshi Ishimoto, Azusa Kamikouchi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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’ attempts to copulate.

Original languageEnglish
Pages (from-to)396-407.e4
JournalCurrent Biology
Issue number3
Publication statusPublished - 2020 Feb 3
Externally publishedYes


  • Drosophila
  • central complex
  • courtship
  • dopamine
  • ellipsoid body
  • feedforward
  • receptivity
  • sexual motivation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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