The characteristics and pharmacology of olfactory cortical LTP induced by theta-burst high frequency stimulation and...

Long-term potentiation (LTP) of monosynaptic excitations in the olfactory cortex slice by theta burst high frequency stimulation (theta-HFS) and application of the metabotropic glutamate receptor-selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) has been studied. Theta-HFS optimally induced LTP when given 4 times at intervals of 20-30 min. The degree of LTP was significantly potentiated by the inclusion of picrotoxin in the perfusion medium but induction was prevented by D-2-amino-5-phosphonopentanoate (25 microM), L-2-amino-3-phosphonopropionate (125 microM), 5-(isoquinolinyl-sulphonyl)-2-methylpiperazine (50 microM), sangivamycin (25 microM) and thapsigargin (1 microM). Of the drugs tested, only D-2-amino-5-phosphonopentanoate failed to depotentiate established LTP. Application of 1S,3R-ACPD (100 microM) repeated 4 times at intervals of 20-30 min also optimally induced an LTP which was significantly less in unstimulated preparations and showed the same pattern of sensitivity to the drugs tested as LTP induced by theta-HFS. It is concluded that the induction of LTP by theta-HFS and 1S,3R-ACPD requires activation of both N-methyl-D-aspartate and metabotropic glutamate receptors and that a protein kinase is essential for the induction and maintenance of LTP. The likely mechanisms of induction and maintenance of olfactory cortical and hippocampal LTP are contrasted.