The type IV-specific phosphodiesterase inhibitor rolipram and its effect on hippocampal long-term potentiation and synaptic tagging

Sheeja Navakkode, Sreedharan Sajikumar, Julietia Uta Frey

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

We investigated the effects of rolipram, a selective cAMP phosphodiesterase (PDE) inhibitor, on late plastic events during functional CA1 plasticity in vitro in rat hippocampal slices. We present data showing that an early form of long-term potentiation (LTP) (early-LTP) that normally decays within 2-3 hr can be converted to a lasting LTP (late-LTP) if rolipram is applied during tetanization. This rolipramreinforced LTP (RLTP) was NMDA receptor and protein synthesis dependent. cAMP formation in region CA1 during late-LTP requires dopaminergic receptor activity (Frey et al., 1989, 1990). Thus, we studied whether RLTP was influenced by inhibitors of the D1,/D5 receptor. Application of the specific D1/D5antagonist SCH23390 (0.1 μM) did not prevent RLTP, suggesting that the phosphodiesterase inhibitor acts downstream of the D1/D5 receptors. We also studied whether rolipram can interact with processes of synaptic tagging, because RLTP was also dependent on protein synthesis, similar to late-LTP. Inhibition of PDE and subsequent induction of RLTP in one synaptic population were able to transform early-LTP into late-LTP in a second, independent synaptic population of the same neurons. This supports our hypothesis that cAMP-dependent processes are directly involved in the synthesis of plasticity-related proteins.

Original languageEnglish (US)
Pages (from-to)7740-7744
Number of pages5
JournalJournal of Neuroscience
Volume24
Issue number35
DOIs
StatePublished - Sep 1 2004

Keywords

  • Functional plasticity
  • Long-term potentiation
  • Phosphodiesterases
  • Protein synthesis
  • Rolipram-reinforced LTP (RLTP)
  • Synaptic tagging

ASJC Scopus subject areas

  • Neuroscience(all)

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