Neuronal nicotinic receptors modulate synaptic function in the hippocampusand are sensitive to blockade by the convulsant strychnine and by the anti-Parkinson drug amantadine

Evidence is provided that rapid application of nicotinic agonists to CA1 in terneurons in hippocampal slices can trigger responses with at least one of three components: (i) whole-cell currents due to activation of nicotinic r eceptors (nAChRs) on the neuron under study; (ii) fast current transients r epresenting back-propagating action potentials; and (iii) post-synaptic cur rents mediated by gamma-aminobutyric acid (GABA) released from presynaptic neurons by activation of preterminal nAChRs. The use of the alpha 7-nAChR-s elective agonist choline and of nAChR-subtype-selective antagonists led to the conclusion that these responses can be mediated by alpha 7 or alpha 4 b eta 2 nAChRs. Experiments carried out in cultured hippocampal neurons demon strated that the evoked GABA release can also be reduced by activation of t hese receptors, and showed that the convulsant strychnine is a competitive antagonist of alpha 7 nAChRs and a non-competitive antagonist of alpha 4 be ta 2 nAChRs, whereas the anti-Parkinson drug amantadine is a non-competitiv e antagonist of alpha 7, alpha 4 beta 2, and alpha 3 beta 4 nAChRs. (C) 199 8 Elsevier Science Ireland Ltd. All rights reserved.