Abstract
The last decade the serotonin (5-hydroxytryptamine; 5-HT) system has received enormous attention due to its role in regulation of behavior, exemplified by the discovery that increased 5-HT tone in the central nervous system is able to alleviate affective disorders. Here, we review the developmental processes, with a special emphasis on subset specification, leading to the formation of the 5-HT system in the brain. Molecular classification of 5-HT neuronal groups leads to the definition of two independent rostral groups positioned in rhombomere 1 and 2/3 and a caudal group in rhombomere 5-8. In addition, more disperse refinement of these subsets is present as shown by the selective expression of the 5-HT1A autoreceptor, indicating functional diversity between 5-HT subsets. The functional significance of the molecular coding differences is not well known and the molecular basis of described specific connectivity patterns remain to be elucidated. Recent developments in genetic lineage tracing models will provide these data and form a major step-up toward the full understanding of the importance of developmental programming and function of 5-HT neuronal subsets.
Highlights
Serotonin is one of the monoamine neurotransmitters in the brain and has a widespread innervation pattern
The importance of the serotonergic transmitter system is exemplified by the association of serotonergic activity with psychiatric disorders like depression, and specific drugs aimed at changing the serotonergic tone, as selective serotonin reuptake inhibitors (SSRIs), are widely used in the clinic to alleviate such psychiatric disorders
Serotonergic neurons are generated in the central nervous system (CNS), born between E10.5 and E12.5 in the mouse (Pattyn et al, 2004), and make up the anatomical locations designated as B1–B9 in the adult brain
Summary
Edited by: Judith Homberg, Radboud University Nijmegen Medical Centre, Netherlands. We review the developmental processes, with a special emphasis on subset specification, leading to the formation of the 5-HT system in the brain. Molecular classification of 5-HT neuronal groups leads to the definition of two independent rostral groups positioned in rhombomere 1 and 2/3 and a caudal group in rhombomere 5-8. The functional significance of the molecular coding differences is not well known and the molecular basis of described specific connectivity patterns remain to be elucidated. Recent developments in genetic lineage tracing models will provide these data and form a major step-up toward the full understanding of the importance of developmental programming and function of 5-HT neuronal subsets
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