The cGMP producing natriuretic peptide receptor B (NPR-B) and its ligand C-type natriuretic peptide (CNP) are widely distributed in the brain and are highly expressed in the hippocampal regions CA1-CA3. To date only limited functional data is available concerning the physiological effects of the peptide hormone ill the hippocampus. Therefore, we were interested in how bath application of the peptide hormone might influence synaptic plasticity following high frequency stimulation (HFS). We found that CNP application decreased the population spike (PS) amplitude after HFS, thereby affecting long-term potentiation (LTP) in acute hippocampal slices. To investigate the molecular consequences of CNP application leading to a decrease in PS amplitude, we further analyzed the impact of the hormone oil the number of presynaptic synapsin I clusters and number off postsynaptic AMPA receptor Subunit GluR1 Clusters as well as their co-localization ill a primary hippocampal cell culture system. The observed pre-and postsynaptic effects after CNP stimulation of the cGMP pathway ill hippocampal cell cultures may underlie the effect of the peptide hormone oil LAP. (C) 2008 Elsevier Inc. All rights reserved.