title: Volatile anesthetic isoflurane inhibits LTP induction of hippocampal CA1 neurons through α4β2 nAChR subtype-mediated mechanisms.
abstract: OBJECTIVE
  Volatile anesthetic isoflurane contributes to postoperative cognitive dysfunction and inhibition of long-term potentiation (LTP), a synaptic model of learning and memory, but the mechanisms are uncertain. Central neuronal α4β2 subtype nicotinic acetylcholine receptors (nAChRs) are involved in the induction of LTP in the hippocampus. Isoflurane inhibits α4β2 nAChRs at concentrations lower than those used for anesthesia. Therefore, we hypothesized that isoflurane-inhibited LTP induction of hippocampal CA1 neurons via α4β2 nAChRs subtype inhibition.
  
  
  METHODS
  Transverse hippocampal slices (400μm thick) were obtained from male rats (6-8 weeks old). Population spikes were evoked using extracellular electrodes by electrical stimulation of the Schaffer collateral-commissural pathway of rat hippocampal slices. LTP was induced using high frequency stimulation (HFS; 100Hz, 1s). Clinically relevant concentrations (0.125-0.5mM) of isoflurane with or without nicotine (nAChRs agonist), mecamylamine (nAChRs antagonist), 3-[2(S)-2-azetidinylmethoxy] pyridine (A85380) and epibatidine (α4β2 nAChRs agonist), dihydro β erythroidine (DHβE) (α4β2 nAChRs antagonist) were added to the perfusion solution 20min before HFS to test their effects on LTP by HFS respectively.
  
  
  RESULTS
  A brief HFS induced stable LTP in rat hippocampal slices, but LTP was significantly inhibited in the presence of isoflurane at concentrations of 0.125-0.5mM. The inhibitive effect of isoflurane on LTP was not only reversible and could be prevented by nAChRs agonist nicotine and α4β2 nAChRs agonist A85380 and epibatidine, but also mimicked and potentiated by nAChRs antagonist mecamylamine and α4β2 nAChRs antagonist DHβE.
  
  
  CONCLUSIONS
  Inhibition of α4β2 nAChRs subtype of hippocampus participates in isoflurane-mediated LTP inhibition.
authors.affiliation: Department of anesthesiology, the first hospital of Jilin university, n(o) 71, Xinmin St, 130021 Changchun, China; School of public health, Jilin university, Changchun 130021, China.
authors.forename: M-H
authors.initials: MH
authors.lastname: Piao
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Y-S
authors.initials: YS
authors.lastname: Wang
authors.forename: J-P
authors.initials: JP
authors.lastname: Qiu
authors.forename: C-S
authors.initials: CS
authors.lastname: Feng
mesh_terms: D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007530:Isoflurane / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*
chemical_list: C104288:A 85380; D018685:Anesthetics, Inhalation; D001384:Azetidines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D009538:Nicotine; D007530:Isoflurane; C082748:epibatidine
keywords: Anesthesia; Anesthésie; Cognitive function; Fonction cognitive; Hippocampe; Hippocampus; Long-term potentiation; Nicotine; Potentialisation à long terme; Receptors; Récepteurs