Neuropeptides regulate a multitude of behaviors in many organisms (Li et al., 2014). However, mechanisms by which functions of neuropeptides are coordinated to generate proper behaviors are not fully understood. In C. elegans, the SMB motor neurons consist of two pair of neurons that innervate head/neck muscles (White et al, 1986) and shape the amplitude of sinusoidal movement (Gray et al, 2005, Kim et al., 2014), indicating a role of SMB in head locomotion. The SMB neurons have shown to express FMRFamide-related neuropeptide FLP-12 (Kim and Li, 2004, Kim et al., 2014). To identify roles of FLP-12 neuropeptide in head locomotive behavior, we first observed phenotypic consequences by loss of FLP-12. We measured five locomotive parameters including omega turn, reversal, head lift, foraging and frequency of head movement. We found that all five locomotive parameters are increased in
flp-12 mutants. We fully rescued defects in head locomotion of
flp-12 mutants by expressing flp-12cDNA specifically in SMB. These results indicate that FLP-12 may act in the SMB to regulate head movement. To identify receptors for FLP-12, we performed RNAi screening against a total of 16 putative neuropeptide receptor genes. We found that knock-down of several genes including
frpr-8 exhibits increases foraging behavior similarly to
flp-12 mutants and
frpr-8 mutants. Expressing
frpr-8 cDNA with its own promoter successfully rescues foraging phenotype of
frpr-8. Heterogously expressed FRPR-8 in HEK cells are sufficient to confer Ca2+ response upon FLP-12 exposure. Altogether, our data expand our understanding of how a single neuropeptide and its receptor modulate behaviors.