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Does serotonin transporter expression influence amygdala activity or fear learning?

Genetic variation in serotonin transporter (SERT) expression in humans is linked to individual differences in personality traits and susceptibility to depression and anxiety. However, large-sample gene-association studies have failed to replicate these findings. Nevertheless, an influential idea is that SERT expression affects reactivity of the amygdala, a key brain structure for emotional processing. However, the link between SERT expression and amygdala reactivity in humans has also been challenged. Thus, at the heart of this debate lie two unanswered questions: Does variation in SERT expression influence emotional processing? If so, what are the underlying neuronal mechanisms? Here, using two different transgenic mouse models (SERT over-expression and SERT knock-out) combined with intra-amygdalar recordings in behaving animals, I show that SERT expression has an unequivocal influence on fear learning, amygdala hemodynamic responses and theta frequency (5-10Hz) neuronal oscillations. Specifically, mice with lower SERT expression learned faster and exhibited greater amygdala hemodynamic responses and increased theta oscillations to aversive cues compared to mice with higher SERT expression. Based on these and other results I will argue that serotonin primarily influences learning rather than mood.