Circular RNAs (circRNAs) are a novel category of noncoding transcripts that, despite their recent discovery, remain largely unexplored. After a circRNA screening, we selected a transcript derived from the Dtnb (Dystrobrevin Beta) gene for functional analysis. This circRNA is of particular interest as it is highly expressed in mouse brain tissue, where its levels are greater than those of the linear isoform generated from the same gene. A more detailed analysis revealed its distribution across distinct brain regions.
To explore the role of circDtnb in vivo, we generated a novel loss-of-function transgenic mouse line, subsequently characterized electrophysiologically. Patch-clamp recordings in CA1 pyramidal neurons from hippocampal slices showed preserved intrinsic properties but altered synaptic features. Stimulation of Schaefer collateral inputs revealed reduced facilitation in neurons of the transgenic animals, observed by stimulating with 2 pulses and quantifying the paired-pulse ratio, as well as when stimulating with a train-of-pulses. This finding was accompanied by an increased frequency of mEPSCs, which jointly suggests enhanced vesicular release probability. As this phenotype could be explained by fewer synaptic contacts, we are performing analyses of neuronal morphology and dendritic spine density.
The electrophysiological characterization of the circDtnb KO mouse aims to provide valuable insights into the biological role of this circRNA.