PKA controls calcium influx into motor neurons during a rhythmic behavior.

Cyclic adenosine monophosphate (cAMP) has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine) rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR) signaling pathway that is dependent on cAMP. Here, we show that the C. elegans catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that duanyu1529 is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active duanyu1529 transgenes reveals that knockdown of duanyu1529 activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive duanyu1529 activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that duanyu1529 activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active duanyu1529 increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of duanyu1529 to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that duanyu1529 activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels.

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