title: The native serotonin 5-HT(5A) receptor: electrophysiological characterization in rodent cortex and 5-HT(1A)-mediated compensatory plasticity in the knock-out mouse.
abstract: The 5-HT(5A) receptor is the least understood serotonin (5-HT) receptor. Here, we electrophysiologically identify and characterize a native 5-HT(5A) receptor current in acute ex vivo brain slices of adult rodent prefrontal cortex. In the presence of antagonists for the previously characterized 5-HT(1A) 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-HT(5A) antagonist, SB-699551, and are not observed in 5-HT(5A) receptor knock-out mice. Further characterization reveals that the 5-HT(5A) 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-HT(5A) receptor results in an unexpected, large increase in the inhibitory 5-HT(1A) receptor currents. The presence of functional prefrontal 5-HT(5A) receptors in normal rodents along with compensatory plasticity in 5-HT(5A) receptor knock-out mice testifies to the significance of this receptor in the healthy prefrontal cortex.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Goodfellow
authors.forename: Craig D C
authors.initials: CD
authors.lastname: Bailey
authors.forename: Evelyn K
authors.initials: EK
authors.lastname: Lambe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004558:Electric Stimulation; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000172:deficiency / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D058786:GABA-B Receptor Agonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D026941:Sodium Channel Blockers; C078730:serotonin 5 receptor; C024986:barium chloride; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D013779:Tetrodotoxin; D001418:Baclofen