title: Evidence for postsynaptic induction and expression of NMDA receptor independent LTP.
abstract: Whole cell/patch-clamp and extracellular field potential recordings were used to study the induction and expression of N-methyl-D-aspartate (NMDA) receptor independent long-term potentiation (LTP) in area CA1 of the in vitro rat hippocampus. Induction of NMDA receptor independent LTP was prevented by manipulations that inhibited postsynaptic depolarization during tetanic stimulation: direct hyperpolarization of postsynaptic neurons and bath application of an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptor antagonist. NMDA receptor independent LTP also was blocked by intracellular application of the lidocaine derivative, N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314), to CA1 pyramidal neurons. These results complement the previous findings that NMDA receptor independent LTP was inhibited by postsynaptic injections of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and also was inhibited by a L-type voltage-dependent calcium channel antagonist (nifedipine). Collectively, these data make a strong case for the postsynaptic induction of this form of LTP. This paper also provides evidence for postsynaptic expression of NMDA receptor independent LTP. In an experiment where AMPA- and NMDA-receptor-mediated excitatory postsynaptic potentials (EPSPs) were isolated pharmacologically, LTP was found for only the AMPA-receptor-mediated EPSPs. In a separate experiment, paired-pulse facilitation (PPF) was measured during NMDA receptor independent LTP. Although there was an initial decrease in PPF, suggesting a posttetanic increase in the probability of glutamate release, the change in PPF decayed within 30-40 min of the tetanic stimulation, whereas the magnitude of the LTP was constant over this same time period. In addition, the LTP, but not the corresponding change in PPF, was blocked by the metabotropic glutamate receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine. These results are accounted for most easily by a selective increase in postsynaptic AMPA receptor function, but one type of presynaptic modification-an increase in the number of release sites without an overall change in the probability of release-also could account for these results (assuming that the level of glutamate release before LTP induction fully saturated NMDA, but not AMPA, receptors). One possible presynaptic modification, an increase in axon excitability, was ruled out by analysis of the presynaptic fiber volley, which was not increased at any time after LTP induction.
authors.affiliation: Department of Physiology, Marshall University School of Medicine, Huntington, West Virginia 25755-9340, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Grover
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C012647:QX-314; C056723:FG 9041; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008012:Lidocaine