Dopamine receptor DOP-1 engages a sleep pathway to modulate swimming inC. elegans

Summary Animals require robust yet flexible programs to support locomotion. While it is clear that a variety of processes must be engaged to ensure rhythmic actions, the exact mechanisms remain largely unknown. Here we report a novel pathway that connects the D1-like dopamine receptor DOP-1 with a sleep mechanism to modulate swimming in C. elegans . We show that DOP-1 plays a negative role in sustaining swimming behavior. By contrast, a pathway through the D2-like dopamine receptor DOP-3 negatively regulates the initiation of swimming, but its impact fades quickly over a few minutes. We find that DOP-1 and the GPCR kinase GRK-2 function in the sleep interneuron RIS, where DOP-1 modulates the secretion of a sleep neuropeptide FLP-11. Our genetic studies further show that DOP-1 and FLP-11 act in the same pathway to modulate swimming. Together, these results delineate a functional connection between a dopamine receptor and a sleep program to regulate swimming in C. elegans . The temporal transition between DOP-3 and DOP-1 pathways highlights the dynamic nature of neuromodulation for rhythmic movements that persist over time. HIGHLIGHTS The D1-like dopamine receptor DOP-1 regulates swimming at 10 minutes An integrated function of DOP-1 and DOP-3 is required for the continuity of swimming DOP-1 and GRK-2 act in the sleep neuron RIS FLP-11, a neuropeptide that promotes sleep, negatively regulates swimming IN BRIEF Xu et al. investigated genetic programs that modulate swimming behavior in the nematode C. elegans . They identified a functional link that couples a D1-like dopamine receptor to a sleep program that modulates the sustained phase rather than the initial phase of swimming.