PACAP-38 enhances excitatory synaptic transmission in the rat hippocampal CA1 region

Specific receptors for pituitary adenylate cyclase-activating polypeptide ( PACAP), a novel peptide with neuroregulatory and neurotrophic functions, ha ve been identified recently in different brain regions, including the hippo campus. In this study, we examined the effects of PACAP-38 on the excitator y postsynaptic field potentials (fEPSPs) evoked at the Schaffer collateral- CA1 synapses. Brief bath application of PACAP-38 (0.05 nM) induced a long-l asting facilitation of the basal transmission. Enhancement of this response was occluded in part by previous high-frequency-induced long-term potentia tion (LTP). PACAP-38 did not significantly alter the paired-pulse facilitat ion (PPF). PACAP-38 has been shown to have a presynaptic effect on the sept ohippocampal cholinergic terminals, which results in an increase in basal a cetylcholine (ACh) release. To assess whether the PACAP-38 enhancement of C A1 synapses was related to the activation of the cholinergic system we exam ined the effect of this peptide in the presence of atropine, a muscarinic r eceptor antagonist. The enhancement of the fEPSPs by PACAP-38 was blocked b y bath application of atropine. These results show that PACAP-38 induces fa cilitation of hippocampal synaptic transmission through activation of the c holinergic system via the muscarinic receptors.