Phosphodiesterase 4B (PDE4B) and cAMP-level regulation within different tissue fractions of rat hippocarnpal slices during long-terin potentiation in vitro

Molecular events associated with mnemonic processes and neuronal plasticity are postulated to result in functional changes in synaptic structure. One possible site is the post-synaptic density, where activity-dependent changes modulate signal transduction cascades, In this report, we detail spatial-temporal changes for phosphodiesterase 4B (PDE4B) proteins and their Substrate cAMP within three neuronal fractions during early and late long-term potentiation (LTP). The cAMP-dependent protein kinase A cascade which can be regulated by distinct PDE4B activity - is required for mnemonic processes as well as mechanisms or neuronal plasticity, such as those during the maintenance or late-LTP. Fluorescence in situ hybridization studies (FISH) identified no translocation of PDE4B3 from the soma after late-LTP induction indicating a subtle, local control of PDE413 activity. Protein changes were detected within the PSD-enriched fraction. From these results, we conclude that either the changes in PDE413 are due to modulation of pre-existing mRNA, or that the protein is specifically translocated to activated synaptic structures. Furthermore, we report late changes in cAMP levels in the somato-dendritic fraction and discuss this result with the increased PDE4B1/3 doublet in the PSD-enriched fraction. (c) 2005 Elsevier B.V. All rights reserved.