The serotonin 5-HT3 receptor: a novel neurodevelopmental target

Abstract

Serotonin (5-hydroxytryptamine, 5-HT), next to being an important neurotransmitter, recently gained attention as a key-regulator of pre- and postnatal development in the mammalian central nervous system (CNS). Several receptors for 5-HT are expressed in the developing brain including a ligand-gated ion channel, the 5-HT3 receptor. Over the past years, evidence has been accumulating that 5-HT3 receptors are involved in the regulation of neurodevelopment by serotonin. Here, we review the spatial and temporal expression patterns of 5-HT3 receptors in the pre- and early postnatal rodent brain and its functional implications. First, 5-HT3 receptors are expressed on GABAergic interneurons in neocortex and limbic structures derived from the caudal ganglionic eminence. Mature inhibitory GABAergic interneurons fine-tune neuronal excitability and thus are crucial for the physiological function of the brain. Second, 5-HT3 receptors are expressed on specific glutamatergic neurons, Cajal–Retzius cells in the cortex and granule cells in the cerebellum, where they regulate morphology, positioning, and connectivity of the local microcircuitry. Taken together, the 5-HT3 receptor emerges as a potential key-regulator of network formation and function in the CNS, which could have a major impact on our understanding of neurodevelopmental disorders in which 5-HT plays a role.

Serotonin induces the migration of PC12 cells via the serotonin receptor 6/cAMP/ERK pathway

“…5-HT 3 and 5-HT 6 are proposed as candidates to modulate neural migration (30). Although we observed an effect of 5-HT 6 but not 5-HT 3 on PC12 migration, it is possible 5-HT 3 also modulated the PC12 cell migration in different conditions, such as in the presence of NGF.…”

Activation of Human 5-Hydroxytryptamine Type 3 Receptors via an Allosteric Transmembrane Site

“…Human 5-HT 3 Rs are thought to play a role in gastrointestinal function, in nociception, neurodevelopment, and in a variety of psychiatric disorders (Lummis, 2012;Engel et al, 2013;Thompson, 2013). As a consequence, they are important targets for therapeutic drug discovery.…”

Does serotonin deficit mediate susceptibility to ADHD?

“…PET studies on Rhesus monkeys have revealed that clinically relevant doses of Atomoxetine, the treatment drug for depression and ADHD, are capable of occupying both NET and SERT upto a range of >85% for SERT in a dose-dependent manner (Ding YS et al, 2014). 5-HTR3A controls neuronal migration and 5-HTR6 regulate dendritic differentiation (Engel et al, 2013). 5-HTR3…”