AUTHOR=Rojas Paulina S. , Fiedler Jenny L. 

TITLE=What Do We Really Know About 5-HT1A Receptor Signaling in Neuronal Cells?

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=10

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00272

DOI=10.3389/fncel.2016.00272

ISSN=1662-5102

ABSTRACT=<p>Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT<sub>1A</sub> receptor (5-HT<sub>1A</sub>R), specially contrasting with those findings obtained in neuronal cells. The 5-HT<sub>1A</sub>R is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT<sub>1A</sub>R differs from other 5-HT receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by G<sub>α</sub> isoforms and some cascades involve βγ signaling. The activity of 5-HT<sub>1A</sub>R usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca<sup>2+</sup>, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT<sub>1A</sub>R induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and phosphoinositide-3-kinase (PI3K)-Akt signaling pathways. Advances in understanding the actions of 5-HT<sub>1A</sub>R and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.</p>