title: Nicotine-induced switch in the nicotinic cholinergic mechanisms of facilitation of long-term potentiation induction.
abstract: Nicotine facilitates the induction of long-term potentiation (LTP) in the hippocampal CA1 region. The present study reveals the potential mechanisms underlying this effect of nicotine. Timed ACh-mediated activation of alpha7 nicotinic acetylcholine receptors (nAChRs) on pyramidal cells is known to promote LTP induction. Nicotine could suppress this timing-dependent mechanism by desensitizing nAChRs. Timed ACh-mediated activation of alpha7 nAChRs on feedforward interneurons can prevent LTP induction by inhibiting pyramidal cells. Nicotine diminished this ACh-mediated inhibition by desensitizing alpha7 nAChRs, thereby reducing the inhibitory influence on pyramidal cells. In addition to these desensitizing effects, nicotine activated presynaptic non-alpha7 nAChRs on feedforward interneurons to decrease the evoked release of gamma-aminobutyric acid (GABA) onto pyramidal cells. Furthermore, nicotine increased the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) in pyramidal cells, and concomitantly caused a reduction in the size of responses to focal GABA application onto the dendrites of pyramidal cells, suggesting that the nicotine-induced increase in interneuronal activity leads ultimately to a use-dependent depression of evoked IPSCs in pyramidal cells. These nicotine-induced suppressions of inhibition of pyramidal cells were accompanied by enhanced N-methyl-D-aspartate (NMDA) responses in pyramidal cells. Thus, our results suggest that nicotine promotes the induction of LTP by diminishing inhibitory influences on NMDA responses while suppressing the ACh-mediated mechanisms. These ACh-independent mechanisms probably contribute to the nicotine-induced cognitive enhancement observed in the presence of cholinergic deficits, such as those in Alzheimer's disease patients.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Jia
authors.forename: Naoya
authors.initials: N
authors.lastname: Hamaue
authors.forename: Katumi
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000633:toxicity; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D003714:Denervation / Q000379:methods; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D000922:Immunotoxins / Q000633:toxicity; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009699:N-Glycosyl Hydrolases; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000110:Acetylcholinesterase; D000157:Aconitine; D000911:Antibodies, Monoclonal; D004079:Dihydro-beta-Erythroidine; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010721:Phosphinic Acids; D010852:Picrotoxin; D011412:Propanolamines; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014633:Valine; D005680:gamma-Aminobutyric Acid; C085696:192 IgG-saporin; C085075:CGP 55845A; C054634:methyllycaconitine; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid