Serotonin induces tonic firing in layer V pyramidal neurons of rat prefrontal cortex during postnatal development.
The effects of serotonin (5-HT) on neuronal activity were examined during postnatal development in layer V pyramidal neurons of the rat prefrontal cortex (PFC) in vitro. Whole-cell patch-clamp recordings were made in slices obtained from rats aged between postnatal day (P) 6 and P31. In P14 or younger neurons, bath application of 5-HT (10 microM) induced a large depolarization followed by tonic firing at 2-5 Hz. The excitatory effects of 5-HT decreased rapidly after P14, so that by P21, 5-HT produced a small depolarization or hyperpolarization without cell firing. The excitatory effects of 5-HT at younger ages were attributed to 5-HT2A receptors because the effects were mimicked by the 5-HT2 agonist alpha-methyl-5-HT but not by the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide, nor by the 5-HT2B/2C agonist 1-(3-chlorophenyl)piperazine, and were blocked by the 5-HT2A antagonists ketanserin and alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol. The excitatory responses persisted in 0 [Ca2+]o and high [Mg2+]o in the presence of TTX or blockers of ionotropic glutamate receptors, suggesting that the effects were mediated essentially by postsynaptic mechanisms. The responses to 5-HT involve a reduction of K+ conductance and an enhancement of the hyperpolarization-activated Na+/K+ current. The developmental decline of 5-HT-induced excitatory effects was associated with a downregulation of 5-HT2A receptor function and a decrease in the input resistance during early life. These results suggest that 5-HT is an important regulator of neuronal activity in the neonatal PFC and may play a role in activity-dependent developmental processes.
Zhang
Zhong-Wei
ZW
Centre de Recherche Université Laval Robert-Giffard, Département de Psychiatrie, Faculté de Médicine, Université Laval, Québec City, G1J 2G3, Canada. zhongwei.zhang@crulrg.ulaval.ca
D000367:Age Factors; D000818:Animals; D015536:Down-Regulation; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; D012701:Serotonin; D007650:Ketanserin