Nicotinic receptors on hippocampal cultures can increase synaptic glutamate currents while decreasing the NMDA-receptor component

Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) can en hance the release of glutamate from synapses in hippocampal slices and cult ures. In hippocampal cultures making autaptic connections, rapid applicatio n of a high concentration of nicotine activated presynaptic, postsynaptic, and somatic nAChRs, which consequently enhanced the amplitude of evoked exc itatory postsynaptic currents (eEPSCs) mediated by glutamate receptors. The increased eEPSC amplitudes arose from enhanced glutamate release caused by presynaptic nAChRs (Radcliffe and Dani, 1998, Journal of Neuroscience 18, 7075). The same whole-cell nicotine applications that enhanced non-NMDA eEP SCs often decreased the NMDA-receptor component of the eEPSCs. Furthermore, whole-cell activation of nAChRs by nicotine selectively reduced the amplit ude of the whole-cell NMDA-receptor currents without affecting the non-NMDA receptor currents. The inhibition by nicotine was prevented by the alpha7- specific antagonist, methyllycaconitine, and required the presence of extra cellular Ca2+. The calmodulin antagonist fluphenazine prevented inhibition of the NMDA-receptor current by nAChR activity, suggesting that a Ca2+-calm odulin-dependent process mediated the effect of nicotine. Our results indic ate that activation of nAChRs can modulate glutamatergic synapses in severa l ways. Presynaptic nAChR activity enhances synaptic transmission by increa sing transmitter release. Additionally, somatic or postsynaptic nAChRs can initiate a Ca2+ signal that can act via calmodulin to reduce the responsive ness of NMDA receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.