Multiple p38/JNK Mitogen-activated protein kinase (MAPK) signaling pathways mediate salt chemotaxis learning in C. elegans.

Animals are able to adapt their behaviors to their environment. In order to achieve this, the nervous system plays integrative roles, such as perception of external signals, sensory processing, and behavioral regulations via various signal transduction pathways. Here genetic analyses of C. elegans found that mutants of components of JNK and p38 Mitogen-activated protein kinase (MAPK) signaling pathways, also known as stress-activated protein kinase (SAPK) signaling pathways, exhibit various types of defects in the learning of salt chemotaxis. C. elegans homologues of JNK MAPKKK and MAPKK, MLK-1 and MEK-1, respectively, are required to avoid salt concentrations experienced during starvation. In contrast, homologues of p38 MAPKKK and MAPKK, NSY-1 and SEK-1, respectively, are required for high-salt chemotaxis after conditioning. Genetic interaction analyses suggest that a JNK family MAPK, KGB-1, functions downstream of both signaling pathways to regulate salt chemotaxis learning. Furthermore, we found that the NSY-1/SEK-1 pathway functions in sensory neurons, ASH, ADF, and ASER, to regulate the learned high-salt chemotaxis. A neuropeptide, NLP-3, expressed in ASH, ADF, and ASER neurons, and a neuropeptide receptor, NPR-15, expressed in AIA interneurons that receive synaptic input from these sensory neurons, function in the same genetic pathway as NSY-1/SEK-1 signaling. These findings suggest that this MAPK pathway may affect neuropeptide signaling between sensory neurons and interneurons, thus promoting high-salt chemotaxis after conditioning.