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.
Highlights
In addition to its role as a classical neurotransmitter, it is well established that serotonin (5-hydroxytryptamine, 5-HT) plays a pivotal role in the development of the mammalian central nervous system (CNS). 5-HT is one of the first neurotransmitters to appear during development (E13 in the rat, Lauder, 1990; and E11 in the mouse, Pfaar et al, 2002) and acts a neurotrophic factor in early embryonic CNS development and even before synapse formation of cortical neurons is completed
We summarize those recent findings which suggest that 5-HT3 receptors emerge as a novel target during the development of the CNS
Ubiquitous post-/extra- and presynaptic expression of 5HT3 receptors was recently observed in glutamatergic granule cells of the cerebellum within the first three postnatal weeks in rodents (Oostland et al, 2011, 2013). 5-HT3 receptors are important for the serotonergic regulation of short-term synaptic plasticity at parallel fiber-Purkinje cell synapses during the early postnatal sensitive period and regulate the maturation state of these synapses (Oostland et al, 2011)
Summary
In addition to its role as a classical neurotransmitter, it is well established that serotonin (5-hydroxytryptamine, 5-HT) plays a pivotal role in the development of the mammalian central nervous system (CNS). 5-HT is one of the first neurotransmitters to appear during development (E13 in the rat, Lauder, 1990; and E11 in the mouse, Pfaar et al, 2002) and acts a neurotrophic factor in early embryonic CNS development and even before synapse formation of cortical neurons is completed. 5-HT3 receptor-expressing neuroblasts are present in several locations in the early postnatal and adult brain Both the regulation of migration and maturation of embryonic CGE- and adult SVZ-derived neuroblasts as well as the functional role of 5-HT3 receptors during these processes are yet unresolved. It was recently reported that electrophysiological activity is essential for the postnatal correct migration and axonal and dendritic integration of CGE-derived reelin- and CR-, but not VIP-positive neurons (García et al, 2011). Whereas this activity is glutamate-dependent after P3, the source of activity before P3 is yet unclear. Serotonergic input via 5-HT3 receptors might be a candidate source of such perinatal activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
