Serotonin and Catecholamines Neuronal Circuits regulate opposing behaviors in C.elegans

BLANCO, MARÍA GABRIELA; GIUNTI SEBASTIÁN; DIEGO HERNAN RAYES; MARÍA JOSÉ DE ROSA

Congreso; XXXII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS.; 2018

Patients with anxiety disorders, such as post-traumatic stress disorders (PTSD) and panic attacks,exhibit high levels of catecholamines (CA), even in the absence of stress. Selective serotonin (5-HT) reuptake inhibitors (SSRIs), which increase the 5-HT level in the synaptic gap, are the mostsuitable drugs to treat these patients. This means 5-HT plays an important role in these disorders,but its relationship with CA is still unknown and difficult to study in the complex human nervoussystem. Given its simplicity and the highly conserved neurological pathways, C. elegans can beused to provide insights into the crosstalk between 5-TH and CA.When C. elegans encounters food, it releases 5-HT to inhibit locomotion. We exposed tdc-1 andtbh-1 null mutants (unable to synthetize the analogous of mammalian CA tyramine (TA) andoctopamine (OA), respectively) to exogenous 5-HT and found that they are hypersensitive toparalysis. These results strongly suggest that 5-HT acts antagonistically to CA. In addition, westudied the hypersensitivity to exogenous 5-HT of mutants in TA and OA receptors. We observedthat tyra-3, ser-3 and ser-6 null mutants do not recover completely from the serotonin-inducedparalysis. We are now digging into the molecular and cellular underpinning of these antagonisticeffects by analyzing mutants in 5-HT receptors. These opposite actions could be conserved inmammals and explain the efficiency of SSRIs in PTSD and panic attack treatments.