The serotonin 5-HT₃ receptor: a novel neurodevelopmental target

• ¹Center for NeuroScience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
• ²Max Planck Institute of Psychiatry, Munich, Germany

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.