Interactions of glutamate receptor agonists with long-term potentiation inthe rat hippocampal slice

Previous work has described the apparent desensitisation of neuronal networ ks in the rat neocortex to amino acid agonists, following prior exposure se veral 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 th e 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 apar t, 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 c hanges were obtained of e.p.s.p. size. Tn order to localise the cellular si tes of these changes, agonists were also applied by microiontophoresis to t he cell bodies or dendritic regions of CA1 neurones. Responses to quinolini c acid showed apparent desensitisation at both sites, whereas no decrease w as observed in responses to NMDA or AMPA application. The induction of long -term potentiation again produced a decrease in the size of responses to NM DA and AMPA. Inhibition of nitric oxide (NO) synthase prevented the long-te rm potentiation-induced loss of responsiveness to NMDA, but not AMPA, imply ing a role for NO in the loss of NMDA sensitivity. Recordings of single cel l activity during the iontophoretic application of agonists and induction o f long-term potentiation showed that responses to NMDA were often suppresse d to a greater extent than to quinolinic acid. The results indicate that lo ng-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. (C) 2000 Elsevier Science B.V. All rights res erved.