The foraging gene coordinates brain and heart networks to modulate socially cued interval timing in Drosophila

The foraging gene (for) regulates behavioral plasticity and decision-making, influencing adaptive behaviors such as foraging, learning, and memory. In Drosophila melanogaster, we explore its role in interval timing behaviors, particularly mating duration. Two allelic variants, rover (for^R) and sitter (for^S), exhibit distinct effects: for^R disrupts shorter mating duration (SMD) but not longer mating duration (LMD), while for^S impairs LMD but not SMD. Transheterozygotes (for^R/for^S) disrupt both behaviors, revealing complex allelic interactions. Using single-cell RNA sequencing and knockdown experiments, we identify foraging expression in Pdfr-positive neurons and fru-positive heart cells as critical for LMD. While the gene is expressed in memory-related brain regions, its impact on LMD is mediated through peptidergic signaling and calcium dynamics in the heart. Social context-dependent calcium fluctuations, observed via CaLexA signals, are disrupted by foraging or Pdfr knockdown, impairing LMD. These findings highlight the foraging gene’s role in integrating social cues with physiological states. This study demonstrates the foraging gene’s pleiotropic roles in regulating interval timing through neural and non-neural mechanisms, offering insights into the genetic and environmental interplay underlying adaptive behaviors.