Guanylate cyclases link serotoninergic signaling to modulate ethanol-induced food intake in C. elegans

Ethanol affects the nervous system of animals to cause a boost of feeding, sexual, verbal, and locomotor behaviors. To understand the neural mechanisms of these ethanol-induced behaviors, we investigated a neural pathway of ethanol-induced feeding behavior by guanylate cyclases and serotonin signals in C. elegans. We recorded the intracellular calcium signaling of seven sensory neurons in response to ethanol, and only found a significant increase of calcium signaling in BAG among the seven sensor neurons. And both guanylate cyclases GCY-31 and GCY-33 were crucial signaling protein of calcium response in BAG neurons. In addition, serotonin, released from NSM motor neurons, promoted feeding behavior under ethanol stimulation. And the rescue experiment of double mutant indicated the guanylate cyclases and serotonin in the same signaling pathway. So BAG neurons respond to alcohol through the promotion of intracellular calcium signaling, and then the downstream motor neurons NSM release serotonin to regulate the feeding behavior in C. elegans. These findings revealed a neural circuit to understand how the nervous system responds to ethanol and generates corresponding behavior.