Synaptic transmission at nicotinic acetylcholine receptors in rat hippocampal organotypic cultures and slices

Abstract

1 Whole-cell clamp recordings of the compound synaptic current elicited by afferent stimulation of Schaffer collaterals showed that blockade of the NMDA, AMPA and GABA_A receptor-mediated components by 6-nitro-7-sulphamoyl- benzo(f)quinoxaline-2,3-dione (NBQX), 3-((R)-2-carboxypiperazine-4-yl)propyl-1-phosphonate (R-CPP) and picrotoxin, respectively, left a small residual current in 39 out of 41 CA1 pyramidal neurones in organotypic cultures and 9 out of 16 CA1 cells in acutely prepared slices. 2 This current represented 2.9 ± 0.4% of the compound evoked synaptic response in organoypic cultures and 1.4 ± 0.5% in slices. It was characterized by a slightly rectifying I–V curve and a reversal potential of 3.4 ± 5.1 mV. 3 This residual current was insensitive to blockers of GABA_B, purinergic, muscarinic and 5-HT3 receptors, but it was essentially blocked by the nicotinic receptor antagonist d-tubocurarine (91 ± 4% blockade; 20 μm), and partly blocked by α-bungarotoxin (200 nm) and methyllycaconitine (10 nm), two antagonists with a higher selectivity for α7 subunit-containing nicotinic receptors (48 ± 3% and 55 ± 11% blockade, respectively). 4 The residual current was of synaptic origin, since it occurred after a small delay; its amplitude depended upon the stimulation intensity and it was calcium dependent and blocked by the sodium channel antagonist tetrodotoxin. 5 We conclude that afferent stimulation applied in the stratum radiatum evokes in some hippocampal neurones a small synaptic current mediated by activation of neuronal nicotinic receptors.