Actions of 5-HT on human neocortical neurones in vitro

Using intracellular recordings, we have studied the action of 5-hydroxytryptamine (5-HT) on slices of human temporal, occipital and frontal cortex maintained 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 microM) was 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 hyperpolarising/depolarising response in two others. No response was detected in three cells. The depolarising response was probably mediated by reducing a resting potassium conductance. Ketanserin (0.1 and 1.0 microM) and spiperone (1 microM) reduced the response indicating that it was likely mediated by 5-HT2A receptors. The hyperpolarising response was associated with the opening of ion channels and was blocked by the selective 5-HT1A receptor antagonist WAY-100635 (100 nM). 5-HT inhibited spontaneous synaptic potentials. This effect was reduced by ketanserin (1 microM) but not by WAY-100635 (100 nM). It is concluded that human neocortical neurones in vitro can be depolarised via 5-HT2A receptors and hyperpolarised via 5-HT1A receptors.