Serotonin depletion affects serotonergic neuronal circuits in adult mice

Serotonin is a neurotransmitter synthesized in two steps with tryptophan hydroxylase 2 (Tph2) as the rate-limiting enzyme and it is implicated in the modulation of numerous physiological processes including mood, sleep, aggressivity and sexual behavior. Serotonergic neurons provide a profuse innervation to the whole CNS. The synthesis of serotonin and the expression of its receptors early in embryonic development, as well as its maternal and placental sources to the foetus, have led to the hypothesis that serotonin could act as a growth regulator in specific developmental events such as neurogenesis, neuronal migration and circuitry formation. However, the precise role of serotonin in specific morphogenetic activities during CNS development remains poorly understood. To address the consequences of time-controlled serotonin depletion on CNS development, we have generated a Tph2 conditional (floxed) allele and used it in combination with a Tph2-GFP knockin mouse line allowing the visualization of serotonergic neurons and fibers (Migliarini et al., 2013). Besides the severe abnormalities in the serotonergic circuitry formation observed in Tph2 knockout mice, serotonin depletion in adult animals induces an increase of the density of serotonergic fibers projecting to the hippocampus. These results show that the mature serotonergic system exhibits a previously unexpected plasticity and that appropriate serotonin homeostasis is crucial not only for proper development of the serotonergic neuronal circuit but also for its maintenance during adulthood. Migliarini et al. Mol Psychiatry 2013 18: 1106-18.