Serotonin neuronal function from the bed to the bench: is this really a mirrored way?

Abstract

Significance Statement Induced pluripotent stem cells (iPSCs) offer a great opportunity to recapitulate both normal and pathological development of brain tissues. Recently, three research teams have developed human-PSC technology and direct somatic cell reprogramming to allow induction of human serotonin (5-HT; 5-hydroxytryptamine) neurons in vitro. While preclinical studies have repeatedly shown that 5-HT suppresses 5-HT neuronal firing activity, one group has tested the effect of 5-HT on the neuronal activity of those 5-HT-like cells and found a paradoxical excitatory action of 5-HT. Here, we argue that few cautions in translational interpretations have to be taken into account. Nonetheless, utilizing patient-derived cells for generating disease relevant cell types truly offers a new and powerful approach for investigating mechanisms playing fundamental roles in psychiatric disorders.