TY - JOUR
T1 - The type IV-specific phosphodiesterase inhibitor rolipram and its effect on hippocampal long-term potentiation and synaptic tagging
AU - Navakkode, Sheeja
AU - Sajikumar, Sreedharan
AU - Frey, Julietia Uta
PY - 2004/9/1
Y1 - 2004/9/1
N2 - 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.
AB - 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.
KW - Functional plasticity
KW - Long-term potentiation
KW - Phosphodiesterases
KW - Protein synthesis
KW - Rolipram-reinforced LTP (RLTP)
KW - Synaptic tagging
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UR - http://www.scopus.com/inward/citedby.url?scp=4444262374&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1796-04.2004
DO - 10.1523/JNEUROSCI.1796-04.2004
M3 - Article
C2 - 15342741
AN - SCOPUS:4444262374
SN - 0270-6474
VL - 24
SP - 7740
EP - 7744
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 35
ER -