The involvement of PACAP/VIP system in the synaptic transmission in the hippocampus

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two closely related peptides, which can activate protein kinase A (PKA). At least three receptors for PACAP and VIP have been identified. The PACAP-specific receptor, PAC1 receptor, exhibits a higher affinity for PACAP than VIP, whereas VIP receptors, VPAC1-R and VPAC2-R, have similar affinities for PACAP and VIP. Both PACAP/VIP and their cognate receptors are highly expressed in the brain, including the hippocampus. Recently, their roles in the regulation of synaptic transmission have begun to emerge. PACAP/VIP can signal through different pathways to regulate N-methyl-D: -aspartate (NMDA) receptors in CA1 pyramidal cells. The activation of VPAC1/2-Rs increases evoked NMDA currents via the cyclic AMP/PKA pathway. However, the activation of PAC1-R stimulates a PLC/PKC/Pyk2/Src signaling pathway to enhance NMDA receptor function in hippocampal neurons. Furthermore, different concentrations of PACAP induce different effects on the both α-amino-3-hydroxy-5-isoxazole-propionic acid-evoked current and basal synaptic transmission by activating different receptors. Their roles in learning and memory are also demonstrated using transgenic mice and pharmacological methods.