Long-lasting potentiation and depression by novel isoproterenol and cholecystokinin 8-S interactions in the dentate gyrus

In the in vitro hippocampal slice, novel interactions of a -adrenergic agonist (l-isoproterenol) and neuropeptide (cholecystokinin 8-S) differentially produce long-lasting modifications in the dentate gyrus. When co-applied, a low concentration of l-isoproterenol (50–75 nM) and cholecystokinin 8-S (1.0 M) produce long-lasting depression of evoked action potentials (i.e., population spikes). In contrast, the same concentration of l-isoproterenol followed by a 30-min wash with artificial cerebrospinal fluid and application of cholecystokinin 8-S produces long-lasting potentiation of evoked action potentials. In neither condition are there corresponding modifications of excitatory post-synaptic potentials. These results indicate that l-isoproterenol and cholecystokinin 8-S temporally interact to differentially produce depression or potentiation of granule cell activation. In contrast to long-lasting modifications produced by continuous application of 1.0 M l-isoproterenol, in which both evoked action potentials and excitatory post-synaptic potentials are affected, the present novel paradigm may modify an extra-synaptic locus.