Actions of 5-HT on human neocortical neurones in vitro

Using intracellular recordings, we have studied the action of 5-hydroxytryp tamine (5-HT) on slices of human temporal, occipital and frontal cortex mai ntained in vitro. The recordings were usually made 1.2 to 1.5 mm down from the pial surface, in or around layer III, The action of 5-HT (30-50 mu M) w as studied on 21 cells (from 12 individuals) which had electrophysiological characteristics of glutamatergic pyramidal neurones. 5-HT depolarised the majority (11) of these cells with a median response of 5 mV. It produced a hyperpolarising response in five neurones (median = -4 mV) and a combined h yperpolarising/depolarising response in two others. No response was detecte d in three cells, The depolarising response was probably mediated by reduci ng a resting potassium conductance. Ketanserin (0.1 and 1.0 mu M) and spipe rone (1 mu M) reduced the response indicating that it was likely mediated b y 5-HT2A receptors. The hyperpolarising response was associated with the op ening of ion channels and was blocked by the selective 5-HT1A receptor anta gonist WAY-100635 (100 nM). 5-HT inhibited spontaneous synaptic potentials. This effect was reduced by ketanserin (1 CGM) but not by WAY-100635 (100 n M). It is concluded that human neocortical neurones in vitro can be depolar ised via 5-HT2A receptors and hyperpolarised via 5-HT1A receptors. (C) 1999 Elsevier Science B.V. All rights reserved.