title: Interactions of glutamate receptor agonists with long-term potentiation in the rat hippocampal slice.
abstract: Previous work has described the apparent desensitisation of neuronal networks in the rat neocortex to amino acid agonists, following prior exposure several minutes earlier. Since long-term potentiation is believed to involve activation of amino acid receptors, we have now sought to determine whether long-term potentiation can modify the sensitivity of neurones to glutamate receptor agonists in rat hippocampal slices. Responses were measured as the change in population spike or postsynaptic potential (e.p.s.p.) size. Two applications of N-methyl-D-aspartate (NMDA), quinolinic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainate, 45 min apart, did not exhibit any apparent desensitisation. However, the induction of long-term potentiation produced a marked loss of sensitivity to quinolinic acid, with smaller effects on NMDA, AMPA and kainate responses. No marked changes were obtained of e.p. s.p. size. In order to localise the cellular sites of these changes, agonists were also applied by microiontophoresis to the cell bodies or dendritic regions of CA1 neurones. Responses to quinolinic acid showed apparent desensitisation at both sites, whereas no decrease was observed in responses to NMDA or AMPA application. The induction of long-term potentiation again produced a decrease in the size of responses to NMDA and AMPA. Inhibition of nitric oxide (NO) synthase prevented the long-term potentiation-induced loss of responsiveness to NMDA, but not AMPA, implying a role for NO in the loss of NMDA sensitivity. Recordings of single cell activity during the iontophoretic application of agonists and induction of long-term potentiation showed that responses to NMDA were often suppressed to a greater extent than to quinolinic acid. The results indicate that long-term potentiation can modify the sensitivity of hippocampal neurones to glutamate receptor agonists, and that differences exist in the pharmacology of NMDA and quinolinic acid.
authors.affiliation: Department of Physiology, The Medical School, University of the West Indies, St. Augustine, Trinidad and Tobago.
authors.forename: F
authors.initials: F
authors.lastname: Youssef
authors.forename: T W
authors.initials: TW
authors.lastname: Stone
authors.forename: J I
authors.initials: JI
authors.lastname: Addae
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D017378:Quinolinic Acid