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Neuroscience of Serotonin – New Vistas

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Serotonin is a monoamine that works as an autacoid in the periphery and as a neurotransmitter in the central nervous system of vertebrates. Although serotonin has been extensively studied during the last 50 years, it remains an enigma to researchers. Serotonin is involved in many kinds of normal and ...

Serotonin is a monoamine that works as an autacoid in the periphery and as a neurotransmitter in the central nervous system of vertebrates. Although serotonin has been extensively studied during the last 50 years, it remains an enigma to researchers. Serotonin is involved in many kinds of normal and pathological behavior, and therefore, it remains in the focus of a large number of researchers: the key word “serotonin” appears in more than 40.000 articles published for the past ten years. Several fundamental achievements in serotonin molecular biology as well as the great number of mouse lines with functional mutations in serotonin-related genes opens up new vistas in the understanding of the role that serotonin plays in brain signaling, behavior regulation and the mechanisms of psychopathologies.

Although serotonin discovery dates back to 1940, several fundamental discoveries in serotonin neuroscience were made at the beginning of the 21st century. Here belongs the discovery of tryptophan hydroxylase 2 (TPH2), the specific and key enzyme of 5-HT synthesis in the brain; the demonstration of 5-HT receptor dimerization and its key role in the feedback mechanism of the regulation of 5-HT release and the sensitivity to antidepressant treatment; the interplay between TPH2 and serotonin transporter (SERT) in the regulation of brain 5-HT levels and resistance to antidepressant treatment; and last but not least, the covalent binding of serotonin to other proteins in a process called serotonylation, that plays a role in different cellular processes, including epigenetic regulation of gene expression via histone modification. However, many of these fundamental findings are scattered over different journals and are not known by the neuroscientific community.

In this Frontiers Research Topic, we aim to collect serotonin-related Original Articles and Reviews in one issue in order to introduce them to a wide range of neuroscientists as well as to revise the role that 5-HT plays in the regulation of brain function and behavior in the light of these last achievements. Particular preference will be given especially (but not exclusively) to papers focusing on:
· Application of genetically modified rodents with mutations in the serotonin-related genes (Tph2, Htr1a, Slc6a4) for verification of the association between these genes and psychopathologies observed in clinical studies;
· Involvement of serotonin in the response to environmental challenges and natural adaptation;
· Interaction between the brain serotonin, gut serotonin, and gut microbiota.


Keywords: Tryptophan hydroxylase, Serotonin transporter, Serotonin receptors, Molecular mechanisms, Brain


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