PT - JOURNAL ARTICLE AU - Nathalie M. Goodfellow AU - Craig D. C. Bailey AU - Evelyn K. Lambe TI - The Native Serotonin 5-HT<sub>5A</sub> Receptor: Electrophysiological Characterization in Rodent Cortex and 5-HT<sub>1A</sub>-Mediated Compensatory Plasticity in the Knock-Out Mouse AID - 10.1523/JNEUROSCI.4849-11.2012 DP - 2012 Apr 25 TA - The Journal of Neuroscience PG - 5804--5809 VI - 32 IP - 17 4099 - http://www.jneurosci.org/content/32/17/5804.short 4100 - http://www.jneurosci.org/content/32/17/5804.full SO - J. Neurosci.2012 Apr 25; 32 AB - The 5-HT5A receptor is the least understood serotonin (5-HT) receptor. Here, we electrophysiologically identify and characterize a native 5-HT5A receptor current in acute ex vivo brain slices of adult rodent prefrontal cortex. In the presence of antagonists for the previously characterized 5-HT1A and 5-HT2 receptors, a proportion of layer V pyramidal neurons continue to show 5-HT-elicited outward currents in both rats and mice. These 5-HT currents are suppressed by the selective 5-HT5A antagonist, SB-699551, and are not observed in 5-HT5A receptor knock-out mice. Further characterization reveals that the 5-HT5A current is activated by submicromolar concentrations of 5-HT, is inwardly rectifying with a reversal potential near the equilibrium potential for K+ ions, and is suppressed by blockers of Kir3 channels. Finally, we observe that genetic deletion of the inhibitory 5-HT5A receptor results in an unexpected, large increase in the inhibitory 5-HT1A receptor currents. The presence of functional prefrontal 5-HT5A receptors in normal rodents along with compensatory plasticity in 5-HT5A receptor knock-out mice testifies to the significance of this receptor in the healthy prefrontal cortex.