ANGIOTENSIN-II BLOCKADE OF LONG-TERM POTENTIATION AT THE PERFORANT PATH-GRANULE CELL SYNAPSE IN-VITRO

Field recordings of evoked excitatory postsynaptic potentials (pEPSPs) were carried out in the granule cell stratum moleculare following sti mulation of the perforant path in rat hippocampal slices. Under contro l conditions tetanic stimulation produced long-term potentiation (LTP) as measured by an increase in the initial slope of the pEPSPs that la sted for at least 1 h. LTP experiments were repeated with 0.5, 5.0, 50 , or 500 nM angiotensin II (AII) present in the bath at the time of te tanization. Induction of LTP was blocked by 50 nM AII; however, normal baseline responses were not affected. At the highest dose tested, 500 nM, a decrease in the amplitude and slope of baseline pEPSPs was obse rved. When the AII AT(1) receptor antagonist losartan was present in t he bath AII inhibition of LTP was blocked. The application of losartan alone had no effect on LTP expression. These findings support previou s results from in vivo studies demonstrating that activation of AT(1) receptors in the dentate gyrus blocks the induction of LTP at the perf orant path-granule cell synapse.