Gain modulation by serotonin in pyramidal neurones of the rat prefrontal cortex.
Serotonin (5-HT) is widely implicated in brain functions and diseases. The vertebrate brain is extensively innervated by 5-HT fibres originating from the brain stem, and 5-HT axon terminals interact with other neurones in complex ways. The cellular mechanisms underlying 5-HT function in the brain are not well understood. The present study examined the effect of 5-HT on the responsiveness of neurones in the neocortex. Using patch-clamp recording in acute slices, we showed that 5-HT substantially increased the slope (gain) of the firing rate-current curve in layer 5 pyramidal neurones of the rat prefrontal cortex. The effect of 5-HT on gain is confined to the range of firing rate (0-10 Hz) that is known to be behaviourally relevant. 5-HT also changed current threshold for spike train generation, but this effect was inconsistent, and was independent of the effect on gain. The gain modulation by 5-HT was mediated by 5-HT2 receptors, and involved postsynaptic mechanisms. 5-HT2-mediated gain increase could not be attributed to changes in the membrane potential, the input resistance or the properties of action potentials, but was associated with a reduction of the afterhyperpolarization and an induction of the slow afterdepolarization. Blocking Ca2+ entry with Cd2+ increased the gain by itself and blocked 5-HT2- mediated gain increase. Buffering [Ca2+](i) with 25 mM EGTA also substantially reduced 5-HT2- mediated gain increase. Noradrenaline, which blocked the afterhyperpolarization, also induced a moderate increase in gain. Together, our results suggest that 5-HT may regulate the dynamics of cortical circuits through multiplicative scaling.
Zhang
Zhong-wei
ZW
Centre de recherche Université Laval Robert-Giffard, Département de psychiatrie, Faculté de médecine, Université Laval, Québec, QC, Canada G1J 2G3. zhongwei.zhang@crulrg.ulaval.ca
Arsenault
Dany
D
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D004594:Electrophysiology; D005439:Flufenamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D007473:Ion Channels; D015221:Potassium Channels; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; C042390:alpha-methylserotonin; D012701:Serotonin; D013779:Tetrodotoxin; D005439:Flufenamic Acid