Serotonin Depletion Affects Development and Maintenance of Serotonergic Neuronal Circuits
Year: 2015
Type: article
Abstract: Serotonin is a neurotransmitter implicated in the modulation \nof several behavioral and physiological processes within the central \nnervous system (CNS) including mood, control of sleep, \nappetite, aggressivity and sexual behavior. In neurons serotonin \nis synthesized in two main steps with tryptophan hydroxylase 2 \n(Tph2) as the rate-limiting enzyme. Serotonergic neurons are \none of the most early born neuronal systems in the mammalian \nbrain and provide a widespread innervation to the whole CNS. \nThe synthesis of serotonin during embryonic development \ntogether with a dynamic expression of serotonergic receptors in \nthe CNS has led to the hypothesis that serotonin could act as a \ngrowth regulator in specific neurodevelopmental events such as \nneurogenesis, neuronal migration and circuitry formation. \nAlthough recent discoveries from animal models and human \ngenetic studies have highlighted the importance of serotonin \nhomeostasis maintenance during CNS development, the precise \nrole of this molecule in specific morphogenetic activities \nremains poorly understood. To address the consequences of \ntime-controlled serotonin depletion on CNS development, we \nhave generated a Tph2 conditional (floxed) allele and used it in \ncombination with a Tph2-GFP knockin mouse line allowing the \nvisualization of serotonergic neurons and fibers1. We were able \nto demonstrate that abrogation of serotonin synthesis in adult \nmice affects the proper serotonergic wiring, thus indicating that \nthe serotonergic system exhibits a previously unexpected plasticity \nin response to serotonin signaling. Our results together with \nprevious observations suggest that appropriate serotonin homeostasis \nis crucial not only for proper development of the serotonergic \nneuronal circuit but also for its maintenance during adulthood.
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2612474587