A heart releasing neuropeptide that synchronizes brain-heart regulation during courtship behavior

Distinct internal states drive varied animal behaviors, yet the mechanisms by which non-neuronal factors encode these states remain largely unknown. Here, we show that cardiac activity regulates internal mating states through a conserved brain-heart axis in male flies and mice. In Drosophila, a ppk23-P1 pathway triggers heart rate acceleration upon female perception via crustacean cardioactive peptide, while the heart secretes ion transport peptide that feeds back onto P1 neurons to enhance courtship. Ejaculation rapidly decreases heart rate via Corazonin, mitigating prolonged tachycardia. In mice, a conserved Substance P-TacR1 pathway modulates courtship. Finally, we developed a computational framework to decode internal mating states from cardiac physiology, revealing distinct cardiac signatures. Our findings unveil a novel role for heart-derived neuropeptides in internal state regulation, elucidate a positive feedback loop between the heart and brain, and demonstrate the evolutionary conservation of the brain-heart axis in orchestrating dynamic behavioral and physiological states.