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

Abstract

Evidence is provided that rapid application of nicotinic agonists to CA1 interneurons in hippocampal slices can trigger responses with at least one of three components: (i) whole-cell currents due to activation of nicotinic receptors (nAChRs) on the neuron under study; (ii) fast current transients representing back-propagating action potentials; and (iii) post-synaptic currents mediated by gamma-aminobutyric acid (GABA) released from presynaptic neurons by activation of preterminal nAChRs. The use of the alpha7-nAChR-selective agonist choline and of nAChR-subtype-selective antagonists led to the conclusion that these responses can be mediated by alpha7 or alpha4beta2 nAChRs. Experiments carried out in cultured hippocampal neurons demonstrated that the evoked GABA release can also be reduced by activation of these receptors, and showed that the convulsant strychnine is a competitive antagonist of alpha7 nAChRs and a non-competitive antagonist of alpha4beta2 nAChRs, whereas the anti-Parkinson drug amantadine is a non-competitive antagonist of alpha7, alpha4beta2, and alpha3beta4 nAChRs.