Phosphodiesterase 4B (PDE4B) and cAMP-level regulation within different tissue fractions of rat hippocampal slices during long-term 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 of 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 PDE4B activity. Protein changes were detected within the PSD-enriched fraction. From these results, we conclude that either the changes in PDE4B 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.
Ahmed
T
T
Department of Neurophysiology, Leibniz-Institute for Neurobiology, Brenneckestrasse 6, D-39118 Magdeburg, Germany.
Frey
J U
JU
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003712:Dendrites / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D017404:In Situ Hybridization, Fluorescence; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D009434:Neural Pathways / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000201:enzymology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology; D013570:Synaptic Membranes / Q000201:enzymology
D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4