Impaired EAT-4 vesicular glutamate transporter leads to defective nocifensive response of caenorhabditis elegans to noxious heat

Abstract

In mammals, glutamate is an important excitatory neurotransmitter. Glutamate and glutamate receptors are found in areas specifically involved in pain sensation, transmission and transduction such as peripheral nervous system, spinal cord and brain. In C. elegans, several studies have suggested glutamate pathways are associated with withdrawal responses to mechanical stimuli and to chemical repellents. However, few evidences demonstrate that glutamate pathways are important to mediate nocifensive response to noxious heat. The thermal avoidance behavior of C. elegans was studied and results illustrated that mutants of glutamate receptors (glr-1, glr-2, nmr-1, nmr-2) behaviors was not affected. However, results revealed that all strains of eat-4 mutants, C. elegans vesicular glutamate transporters, displayed defective thermal avoidance behaviors. Due to the interplay between the glutamate and the FLP-18/FLP-21/NPR-1 pathways, we analyzed the effectors FLP-18 and FLP-21 at the protein level, we did not observebiologically significant differences compared to N2 (WT) strain (fold-change < 2) except for the IK602 strain. The data presented in this manuscript reveals that glutamate signaling pathways are essential to elicit a nocifensive response to noxious heat in C. elegans.