Nicotinic acetylcholine receptor-mediated synaptic potentials in rat neocortex

In the neocortex, fast excitatory synaptic transmission can typically be bl ocked by using excitatory amino acid (EAA) receptor antagonists. In recordi ngs from layer II/III neocortical pyramidal neurons, we observed an evoked excitatory postsynaptic potential (EPSP) or current (EPSC) in the presence of EAA receptor antagonists (40-100 muM D-APV+20 muM CNQX, or 5 mM kynureni c acid) plus the GABA(A)-receptor antagonist bicuculline (BIC, 20 muM). Thi s EAA-antagonist resistant EPSC was observed in about 70% of neurons tested , it had a duration of approximately 20 ms and an amplitude of 61.5+/-6.8 p A at -70 mV (n=35). The EAA-antagonist resistant EPSC current-voltage relat ion was linear and reversed near 0 mV (n=23). The nonselective nicotinic ac etylcholine receptor (nAChR) antagonists dihydro-beta -erythroidine (DH bet aE, 100 muM) or mecamylamine (50 muM) reduced EPSC amplitudes by 42 (n=20) and 33% (n=9), respectively. EPSC kinetics were not significantly changed b y either antagonist. Bath application of 10 muM neostigmine, a potent acety lcholinesterase inhibitor, prolonged the EPSC decay time. EAA-antagonist re sistant EPSCs were observed in the presence of antagonists of metabotropic glutamate, serotonergic (5-HT3) and purinergic (P2) receptors. The EAA-anta gonist resistant EPSC appears to be due in part to activation of postsynapt ic nAChRs. These results suggest the existence of functional synaptic nAChR s on pyramidal neurons in rat neocortex. (C) 2000 Elsevier Science B.V. All rights reserved.