Expression of the specific type IV phosphodiesterase gene PDE4B3 during different phases of long-term potentiation in single hippocampal slices of rats in vitro

Hippocampal long-term potentiation (LTP), the most prominent cellular model for learning and memory formation, consists of phases: early-LTP (<4 h) and late-LTP (>4 h), with the latter dependent upon protein translation and transcription. To explore the molecular processes that might be specifically regulated during late-LTP, we have modified standard electrophysiological and molecular biological methods, which allowed the cloning of activated genes and their products from single hippocampal slices in vitro 8 h after LTP induction. From one such screen we identified a specific type IV phosphodiesterase gene, PDE4B3, the first cAMP-specific phosphodiesterase to be associated with LTP. Previous studies documented an integral role for the cAMP-PKA system in late-LTP and recently, inhibition of cAMP degradation facilitates LTP and ameliorates mnemonic deficits. We now report that PDE4B3 is modulated during LTP phases. Its activation is NMDA-receptor dependent and its transcription is transiently up-regulated 2 h after tetanization. Protein expression peaks 6 h after LTP induction and is rapidly down-regulated at 8 h, whereas cAMP levels decrease during LTP phases. Immunohistochemical studies identified that the majority of type IV phosphodiesterase protein staining is localized to the cell bodies and dendrites of neurones in hippocampal CA1.