Visual Abstract Significance Statement Alterations in brain serotonin (5-HT) levels during development can interfere with neuronal circuitry estab-lishment and contribute to behavioral disturbances in adult life. It remains enigmatic whether wiring patterns can be reshaped by fluctuations of 5-HT content in the adult brain. In this study, we show for the first time that the adult serotonergic circuitry is susceptible to perturbations of serotonin homeostasis. These results provide evidence of life-long requirement of proper 5-HT levels to preserve the serotonergic axonal wiring. New Research March/April 2017, 4(2) e0376-16.2017 1–13 Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron devel-opment and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2 fl ° x conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organi-zation. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.
Napolitano, F., Usiello, A., Migliarini, S., Pratelli, M., Pasqualetti, M., & Pelosi, B. (2017). Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry. Eneuro. https://doi.org/10.1523/eneuro.0376-16.2017