SEROTONIN DEPLETION AFFECTS DEVELOPMENT AND MAINTENANCE OF SEROTONERGIC NEURONAL CIRCUITS

Serotonin is a neurotransmitter implicated in the modulation of several behavioral and physiological processes within the central nervous system (CNS) including mood, control of sleep, appetite, aggressivity and sexual behavior. In neurons serotonin is synthesized in two main steps with tryptophan hydroxylase 2 (Tph2) as the rate-limiting enzyme. Serotonergic neurons are one of the most early born neuronal systems in the mammalian brain and provide a widespread innervation to the whole CNS. The synthesis of serotonin during embryonic development together with a dynamic expression of serotonergic receptors in the CNS has led to the hypothesis that serotonin could act as a growth regulator in specific neurodevelopmental events such as neurogenesis, neuronal migration and circuitry formation. Although recent discoveries from animal models and human genetic studies have highlighted the importance of serotonin homeostasis maintenance during CNS development, the precise role of this molecule in specific morphogenetic activities 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 fibers1. We were able to demonstrate that abrogation of serotonin synthesis in adult mice affects the proper serotonergic wiring, thus indicating that the serotonergic system exhibits a previously unexpected plasticity in response to serotonin signaling. Our results together with previous observations suggest that appropriate serotonin homeostasis is crucial not only for proper development of the serotonergic neuronal circuit but also for its maintenance during adulthood.