CONICET | Buscador de Institutos y Recursos Humanos

Despite the intermodulation between serotonergic and adrenergic signals is crucial throughout the animal kingdom, the molecular and cellular mechanisms underlying this interrelation are poorly understood. When food-deprived worms encounter food, 5-HT is released to slow-down their locomotion and to stimulate pharyngeal pumping. In contrast, Tyramine (TA) and Octopamine (OA), invertebrate counterparts for adrenaline and noradrenaline, stimulates locomotion and decreases pharyngeal pumping. We found that well-fed tdc-1 (unable to synthetize TA and OA) and tbh-1 (unable to synthetize OA) null mutants are hypersensitive to the slowing-down response upon food encounter, resembling starved worms. Moreover, exogenous TA and OA recover the increased slowing-down locomotion of tdc-1 null mutants, suggesting that both CAs act antagonistically to food-related behaviors which depend on 5-HT. Furthermore, our calcium imaging recordings showed that the peak of activity of serotoninergic neurons (ADF and NSM) upon encountering food is significantly higher in a tdc-1 null mutant background. We also found that tdc-1 null mutants are hypersensitive to the paralysis produced by exogenous 5-HT in liquid medium. Therefore, we are using this very simple assay to evaluate the paralysis of the different TA and OA null receptor mutants to identify which receptors are involved in this antagonism. Taken together, these results suggest that TA and OA counteract with 5-HT by driving opposing behaviors and by inhibiting 5-HT release. Our final aim is to decipher the neural circuit and the molecules involved in the reciprocal modulation between CA and 5-HT in C. elegans. Given the conservation in molecular components of these pathways, it is likely that our studies are significant to understand this interrelation in other animals.