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 beta-adrene rgic 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) a nd cholecystokinin 8-S (1.0 mu M) produce long-lasting depression of e voked action potentials (i.e., population spikes). In contrast, the sa me concentration of l-isoproterenol followed by a 30-min wash with art ificial cerebrospinal fluid and application of cholecystokinin 8-S pro duces long-lasting potentiation of evoked action potentials. In neithe r condition are there corresponding modifications of excitatory post-s ynaptic potentials. These results indicate that l-isoproterenol and ch olecystokinin 8-S temporally interact to differentially produce depres sion or potentiation of granule cell activation. In contrast to long-l asting modifications produced by continuous application of 1.0 mu M l- isoproterenol, in which both evoked action potentials and excitatory p ost-synaptic potentials are affected, the present novel paradigm may m odify an extra-synaptic locus.