ABSTRACT
Background Neuroimaging studies have consistently reported that stress-related disorders such as depression and anxiety impinge on the activity of emotion regulation networks, namely in the ventromedial prefrontal cortex (vmPFC). This circuitry is known to be extensively modulated by serotonin and it has been long shown that genetic polymorphisms in the serotonin transporter gene (SLC6A4) are linked to anxiety and depression. vmPFC encompasses different brain regions in terms of cytoarchitecture, activity and connectivity. However, molecular heterogeneity, including microRNAs, within the vmPFC and how these differences affect emotion regulation and behavior have not been elucidated.
Methods Here, we took advantage of recently described polymorphisms in marmoset SLC6A4 gene linked to altered threat responses. Using FACS-sorted cells from different brain regions of genotyped marmosets, we tested the hypothesis that specific molecular changes in the form of microRNA’s in precise regions of the vmPFC underlie these behavioral differences.
Results We showed that microRNA profiling is a good means to assess molecular heterogeneity across cell subsets (NeuN+ versus NeuN- cells) or cortical regions (visual cortex versus vmPFC) in the primate cortex. More importantly, we provided evidence that marmosets bearing different SLC6A4 polymorphisms exhibit distinct miRNAs signatures specifically in vmPFC area 32 neurons, but not in the closely related vmPFC area 25 neurons. Finally, levels of these miRNAs were highly correlated to an anxiety-like score in a test of uncertain threat.
Conclusions These data demonstrate that molecular changes within area 32 likely underlie the differential anxiety-like responses associated with SLC6A4 polymorphisms.
Competing Interest Statement
The authors have declared no competing interest.