Distinct serotonergic pathways to the amygdala underlie separate behavioral features of anxiety

Yu et al. show that at least two distinct serotonergic DRN-to-BA pathways are involved in different aspects of anxiety-related behaviors via different molecular mechanisms. Anxiety-like behaviors in mice include social avoidance and avoidance of bright spaces. Whether these features are distinctly regulated is unclear. We demonstrate that in mice, social and anxiogenic stimuli, respectively, increase and decrease serotonin (5-HT) levels in basal amygdala (BA). In dorsal raphe nucleus (DRN), 5-HT boolean AND vGluT3 neurons projecting to BA parvalbumin (DRN5-HT boolean AND vGluT3-BA(PV)) and pyramidal (DRN5-HT boolean AND vGluT3-BA(Pyr)) neurons have distinct intrinsic properties and gene expression and respond to anxiogenic and social stimuli, respectively. Activation of DRN5-HT boolean AND vGluT3 -> BA(PV) inhibits 5-HT release via GABA(B) receptors on serotonergic terminals in BA, inducing social avoidance and avoidance of bright spaces. Activation of DRN5-HT boolean AND vGluT3 -> BA neurons inhibits two subsets of BA(Pyr) neurons via 5-HT1A receptors (HTR1A) and 5-HT1B receptors (HTR1B). Pharmacological inhibition of HTR1A and HTR1B in BA induces avoidance of bright spaces and social avoidance, respectively. These findings highlight the functional significance of heterogenic inputs from DRN to BA subpopulations in the regulation of separate anxiety-related behaviors.

Automated summary

Yu et al. have found that there are at least two distinct serotonergic pathways involved in different aspects of anxiety-related behaviors, with different molecular mechanisms. Different anxiety-like behaviors are regulated by different subsets of neurons and receptors. These findings are important for understanding the regulation of anxiety-related behaviors.