The role of a brain-enriched circular RNA on the dopaminergic pathway

PANNUNZIO C; SZYCHOWSKI L; GIUSTI S; URBANO FJ; BISAGNO V; REFOJO D

San Luis

Congreso; XXXVIII Annual Meeting of the Sociedad Argentina de Investigación en Neurociencias; 2023

Sociedad Argentina de Investigación en Neurociencias

Among the extensive array of non-coding RNAs, a relatively young subclass known as circular RNAs (circRNAs) has been identified. These transcripts are the products of an alternative mechanism of splicing known as backsplicing. Due to its high expression in the brain and synaptic-enrichment, we have selected a circular transcript derived from the Tulp4 gene (circTulp4) for functional characterization. To do so, we have generated a transgenic mouse line to model circTulp4 loss-of-function in vivo. More recently, we have performed an extensive behavioral characterization of our circTulp4-deficient (CD) mouse line where we have demonstrated that the CD mice present an increase in locomotor activity. Moreover, we observed that CD male mice show an alteration in the reward-related behavior revealed by an increase in the overall sucrose preference index. These results prompted us to explore a potential alteration of the dopaminergic pathway in CD mice. To achieve this, we have conducted new tests to evaluate impulsivity and reward behaviors. In order to examine if there exists a sex difference, we decided to complete the battery of tests also in female mice. Additionally, we have also performed electrophysiological analysis in the medial prefrontal cortex, an area enriched with dopaminergic innervations.The experimental pipeline presented here will allow us to assess whether an alteration of the dopaminergic pathway contributes to the phenotype of circTulp4-deficient mice.