title: Nicotinic receptor-mediated enhancement of long-term potentiation involves activation of metabotropic glutamate receptors and ryanodine-sensitive calcium stores in the dentate gyrus.
abstract: Little is known about the mechanisms underlying the enhancement of long-term potentiation (LTP) by nicotine. In the present study, the mechanisms of nicotinic enhancement of LTP were investigated in the rat dentate gyrus in vitro. Acute application of nicotine enhanced LTP induction, an action requiring activation of alpha7 nicotinic acetylcholine receptors (nAChRs), as it was blocked by the nAChR antagonist methyl-lycaconitine, mimicked by the acetylcholine receptor agonist choline and absent in mutant mice null for alpha7 nAChR. Nicotinic enhancement of LTP was both dependent on N-methyl-D-aspartate receptor activation, as no LTP was induced in the presence of nicotine and an N-methyl-D-aspartate receptor antagonist, and expressed post-synaptically, as no change in paired-pulse ratio accompanied nicotinic enhancement of LTP. The nicotinic-enhanced component of LTP, unlike control LTP, was dependent on activation of metabotropic glutamate receptors (mGluRs), being inhibited by the group I/II antagonist LY341495 and the mGluR5 antagonist MPEP, and also dependent on influx of Ca via L-type Ca channels and release from ryanodine (RyR)-sensitive intracellular stores, being prevented by nifedipine and RyR, respectively. It is suggested that nicotinic activation of the Ca-permeable alpha7 nAChRs fills RyR Ca stores and release of Ca from such stores by high-frequency stimulation via Ca-induced Ca release and activation of mGluRs induces an additional component of LTP which summates with control LTP. Chronic application of nicotine in vivo also enhanced LTP induction in slices and was dependent on activation of mGluRs and Ca release from RyR-sensitive intracellular stores, although acutely applied nicotine was not required for such enhanced LTP.
authors.affiliation: Department of Physiology, Trinity College, Dublin 2, Ireland.
authors.forename: Philip
authors.initials: P
authors.lastname: Welsby
authors.forename: Michael
authors.initials: M
authors.lastname: Rowan
authors.forename: Roger
authors.initials: R
authors.lastname: Anwyl
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D019837:Ryanodine Receptor Calcium Release Channel; D064569:alpha7 Nicotinic Acetylcholine Receptor