SYNAPTIC POTENTIALS MEDIATED VIA ALPHA-BUNGAROTOXIN-SENSITIVE NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT HIPPOCAMPAL INTERNEURONS

Exogenous application of acetylcholine elicits inward currents in hipp ocampal interneurons that are mediated via alpha-bungarotoxin-sensitiv e nicotinic acetylcholine receptors, but synaptic responses mediated v ia such receptors have never been reported in mammalian brain. In the present study, EPSCs were evoked in hippocampal interneurons in rat br ain slices by electrical stimulation and were recorded by using whole- cell voltage-clamp techniques. Nicotinic EPSCs were isolated pharmacol ogically, using antagonists to block other known types of ligand-gated ion channels, and then were tested with either alpha-bungarotoxin or methyllycaconitine, which are selective antagonists for nicotinic acet ylcholine receptors that contain the alpha 7 receptor subunit. Each an tagonist proved highly effective at reducing the remaining synaptic cu rrent. Evoked alpha 7-mediated nicotinic EPSCs also were desensitized by superfusion with 1 mu M nicotine, had extrapolated reversal potenti als near 0 mV, and showed strong inward rectification at positive pote ntials. In several interneurons, methyllycaconitine-sensitive spontane ous EPSCs also were observed that exhibited a biphasic decay rate very similar to that of the alpha 7-mediated evoked response. These studie s provide the first demonstration of a functional cholinergic synapse in the mammalian brain, in which the primary postsynaptic receptors ar e alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors.