Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Rhythmic behaviors rely on biological clocks in pacemakers transmitting timing signals to target tissues.
• In C. elegans, intestinal calcium oscillations trigger rhythmic defecation via GABAergic neurons, but the timing signal and delivery mechanism were unknown.

Purpose of the Study:

• To identify the timing signal released by the pacemaker during the C. elegans defecation motor program.
• To elucidate the mechanism of timing information delivery to downstream GABAergic neurons.

Main Methods:

• Calcium imaging in C. elegans.
• Genetic analysis of neuropeptide signaling.
• In vivo electrophysiology and peptide application.

Main Results:

• Neuropeptide-like protein 40 (NLP-40) is released by the pacemaker and induces calcium transients in GABAergic neurons.
• nlp-40 mutants lack muscle contractions, while pacemaker function remains intact.
• SNT-2/synaptotagmin mediates calcium-dependent NLP-40 release, and AEX-2/GPCR is the NLP-40 receptor on GABAergic neurons.
• NLP-40 and AEX-2 are crucial for rhythmic GABAergic neuron activation.

Conclusions:

• NLP-40 acts as the timing signal, released dependently on calcium, to activate GABAergic neurons.
• The neuropeptide NLP-40, acting via AEX-2, delivers temporal information from pacemakers to downstream neurons for rhythmic behavior execution.