Differential alteration of hippocampal synaptic strength induced by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38).

We investigated the effect of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on synaptic transmission in rat hippocampal slices using extracellular recordings. Brief bath application of PACAP-38 induced a long-lasting depression of transmission at the Schaffer collateral-CA1 synapse while at the same time causing enhancement of the perforant path-granule cell synapse in the dentate gyrus. Depression at the CA1 synapse was not occluded by low frequency-induced long-term depression (LTD), nor was enhancement at the granule cell synapse blocked by previous high frequency-induced long-term potentiation (LTP). Both actions of PACAP-38 could be elicited in the presence of an N-methyl-D-aspartate (NMDA) receptor antagonist, or in the presence of inhibitors of cyclic AMP- or Ca2+-dependent protein kinases, suggesting a novel mechanism of synaptic modulation.