FLP-15 functions through the GPCR NPR-3 to regulate local and global search behaviours in Caenorhabditis elegans

The transition from well-fed to food-deprived conditions in C. elegans triggers a stereotypic exploration behaviour in C. elegans characterised by a temporal decrease in cumulative reorientations. We conducted a screen of neuropeptide mutants and identified several candidates involved in modulating this behaviour. Among these, the neuropeptide FLP-15 emerged as a key regulator. Our observations revealed that FLP-15 regulates the frequency of reversals during foraging through the I2 pharyngeal neuron via the G-protein coupled receptor NPR-3. Mutants lacking either flp-15, npr-3 or both displayed a significant defect in reversal frequency which did not decline temporally unlike in wild-type animals. This study also describes the expression pattern of NPR-3 in a subset of head neurons, predominantly comprising of dopaminergic neurons. Finally, flp-15 expression studies and exogenous dopamine supplementation assays revealed that FLP-15 may regulate exploratory search by modulating dopamine transmission, highlighting a novel neuropeptide-dopamine interaction involved in the control of foraging behaviours.