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

## TL;DR

The foraging gene in fruit flies affects mating duration by coordinating brain and heart activity, showing how genes can influence behavior through multiple systems.

## Contribution

The study reveals a novel role of the foraging gene in integrating social cues with physiological states via neural and non-neural mechanisms.

## Key findings

- The rover and sitter alleles of the foraging gene disrupt different mating duration behaviors in fruit flies.
- Foraging gene expression in Pdfr-positive neurons and fru-positive heart cells is critical for longer mating duration.
- Social context influences heart cell calcium dynamics, which are disrupted by foraging gene or Pdfr knockdown.

## Abstract

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 (forR) and sitter (forS), exhibit distinct effects: forR disrupts shorter mating duration (SMD) but not longer mating duration (LMD), while forS impairs LMD but not SMD. Transheterozygotes (forR/forS) 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.

This study reveals that the foraging gene, traditionally associated with behaviors such as foraging and learning, plays a critical role in interval timing (e.g., regulation of mating duration) in fruit flies (Drosophila melanogaster). Two natural alleles of the gene, rover (forR) and sitter (forS), specifically disrupt sexually experienced-induced shorter mating duration (SMD) and socially competitive-induced longer mating duration (LMD), respectively, while their transheterozygotes (forR/forS) impair both behaviors. Through single-cell RNA sequencing and functional experiments, the study identifies key roles for foraging in Pdfr-positive neurons of the brain’s central complex and fru-positive cells in the heart. Although the gene is expressed in brain regions associated with memory, its effect on LMD depends on peptidergic signaling (via Pdfr) and calcium dynamics in the heart. Social context (e.g., group vs. isolated rearing) regulates calcium fluctuations in heart cells, a process disrupted by foraging or Pdfr knockdown, thereby impairing LMD. These findings uncover a novel mechanism by which the foraging gene integrates social cues with physiological states through neural and non-neural pathways, providing new insights into how genes regulate adaptive behaviors and their interactions with the environment via complex networks.