LONG-LASTING ENHANCEMENT OF SYNAPTIC EXCITABILITY OF CA1 SUBICULUM NEURONS OF THE RAT VENTRAL HIPPOCAMPUS BY VASOPRESSIN AND VASOPRESSIN(4-8)/

Vasopressin (VP) is axonally distributed in many brain structures, inc luding the ventral hippocampus. Picogram quantities of VP injected int o the hippocampus improve the passive avoidance response of rats, pres umably by enhancing memory processes. Vasopressin is metabolized by th e brain tissue into shorter peptides, such as [pGlu(4),Cyt(6)]VP(4-9) and [pGlu(4),Cyt(6)]VP(4-8), which preserve the behavioral activity bu t lose the peripheral activities of the parent hormone. Using brain sl ices, we investigated whether VP or VP(4-8) affects excitatory postsyn aptic potentials (EPSPs) and/or membrane responses to depolarization i n neurons of the CA1/subiculum of the ventral hippocampus. The EPSPs w ere evoked by stimulating the stratum radiatum of the CA1 field; the m embrane responses were elicited by current injections. Exposure of sli ces for 15 min to 0.1 nM solution of these peptides resulted in an inc rease in the amplitude and slope of the EPSPs in 21 neurons (67%) test ed. No consistent change in either the resting membrane potential or t he input resistance of the neurons was observed. The peptide-induced i ncrease in EPSPs reached a maximum 30-45 min after peptide application . In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60-120 min washout period. In the remai ning 7 neurons (33%), the initial increase in EPSPs amplitude was foll owed by a gradual decline to the pre-administration level. The increas e in EPSP amplitude was often, but not always, associated with a decre ase in the threshold and increase in the number of action potentials i n response to depolarizing current injection. Suppression of GABA(A) r eceptor-mediated inhibition and N-methyl-D-aspartate (NMDA) receptor-m ediated excitation did not prevent the effects of VP and VP(4-8) on th e EPSP amplitude or the threshold for action potentials. The results d emonstrate that 0.1 nM concentrations of these neuropeptides can elici t a long-lasting enhancement of the excitability of CA1/subiculum neur ons of the ventral hippocampus to excitatory, glutamatergic synaptic i nput. This novel action of VP and its metabolite in the ventral hippoc ampus may be the physiological action, mediating the memory-enhancing effect of these peptides.