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1 Centre de recherche Université Laval Robert-Giffard, Département de psychiatrie, Faculté de médecine, Université Laval, Québec, Canada
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.
(Received 2 March 2005;
accepted after revision 4 May 2005;
first published online 5 May 2005)
Corresponding author Z. W. Zhang: Centre de recherche U-Laval Robert-Giffard, 2601, de la canardière, F-6500, Québec, QC, Canada G1J 2G3. Email: zhongwei.zhang{at}crulrg.ulaval.ca
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