title: Modulatory effects of S 38232, a non alpha-7 containing nicotine acetylcholine receptor agonist on network activity in the mouse hippocampus.
abstract: Extracellular field potentials (fEPSPs) and whole cell patch-clamp recordings were used to test the effect of S 38232, a newly developed potent non-alpha7 nicotinic acetylcholine receptors (nAChR) agonist, on synaptic transmission in hippocampal slices obtained from adult mice. S 38232 increased the amplitude of fEPSPs, evoked in stratum radiatum by Schaffer collateral stimulation. This effect was potentiated by picrotoxin, suggesting that S 38232 exerts at least in part its effect on GABAergic interneurons. The action of S 38232 was mediated by non-alpha7 containing nAChRs since it was prevented by DHbetaE (1muM) but not by alpha-BTX (100nM). A similar potentiating effect on fEPSPs was observed when nicotine (1muM) was applied to hippocampal slices obtained from alpha7 -/- mice in the presence of picrotoxin. The potentiating effect of S 38232 was probably presynaptic in origin since it was associated with a significant reduction in paired-pulse ratio. In addition, in patch clamp experiments, S 38232 enhanced the frequency (but not the amplitude) of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs, sIPSCs) recorded from CA1 principal cells. Moreover, it enhanced the frequency of miniature IPSCs but not EPSCs, suggesting that it was acting on nAChRs located on presynaptic/pre-terminal regions of GABAergic interneurons. The effect of S 38232 on GABAergic signaling was concentration-dependent with an EC(50) of 43muM. In conclusions, we present evidence that the new nicotine ligand S 38232, by selectively activating non-alpha7 nAChRs located on principal cells and GABAergic interneurons, influences network activity and information processing in the hippocampus.
authors.affiliation: Neurobiology Sector, International School for Advanced Studies (SISSA), Via Beirut 2-4, 34014 Trieste, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lagostena
authors.forename: Laurence
authors.initials: L
authors.lastname: Danober
authors.forename: Sylvie
authors.initials: S
authors.lastname: Challal
authors.forename: Pierre
authors.initials: P
authors.lastname: Lestage
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaër
authors.forename: Caryn
authors.initials: C
authors.lastname: Trocmé-Thibierge
authors.forename: Enrico
authors.initials: E
authors.lastname: Cherubini
mesh_terms: D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology; D014101:Torpedo; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D018679:Cholinergic Agonists; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor