Genetic Analysis of JNK MAPK Signaling in Stress-Induced Avoidance Behavior in C. elegans.

Mitogen-activated protein kinase (MAPK) signaling is a conserved signal transduction pathway broadly implicated in cellular growth, development and stress responses. While prior studies suggest that it is involved in certain forms of stress-induced learning, whether this role is acute during adult learning or represents early developmental effects on adult behaviors remains unclear. Here we show that the c-Jun N-terminal kinase (JNK) MAPK pathway in C. elegans, consisting of mlk-1/MAPKKK, mek-1/MAPKK and kgb-1/MAPK, acts in the nervous system to promote learned bacterial avoidance under mitochondrial stress, with the MAPK phosphatase VHP-1 counteracting it. Mutants of mlk-1, mek-1 and kgb-1 display moderate sensorimotor defects, and KGB-1 depletion throughout the entire larval to young adult stage, but not solely in adulthood or at any specific larval stage, recapitulates learning defects of the kgb-1 mutant. Transient kgb-1 expression in early development rescues the deficits of adult aversive learning, while adult expression fails to restore the behavioral functions. These data suggest that the role of JNK MAPK signaling in stress-induced avoidance behavior is primarily indirect, presumably via regulation of early neural development. Our work calls for a more rigorous examination of the temporal and tissue requirement of gene functions involved in learning and behavior.