Inhibition of PKA anchoring to A-kinase anchoring proteins impairs consolidation and facilitates extinction of contextual fear memories

Ingrid M. Nijholt, Anghelus Ostroveanu, Wouter A. Scheper, Botond Penke, Paul G.M. Luiten, Eddy A. Van der Zee, Ulrich L.M. Eisel

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Both genetic and pharmacological studies demonstrated that contextual fear conditioning is critically regulated by cyclic AMP-dependent protein kinase (PKA). Since PKA is a broad range protein kinase, a mechanism for confining its activity is required. It has been shown that intracellular spatial compartmentalization of PKA signaling is mediated by A-kinase anchoring proteins (AKAPs). Here, we investigated the role of PKA anchoring to AKAPs in different stages of the memory process (acquisition, consolidation, retrieval and extinction) using contextual fear conditioning, a hippocampus-dependent learning task. Mice were injected intracerebroventricularly or intrahippocampally with the membrane permeable PKA anchoring disrupting peptides St-Ht31 or St-superAKAP-IS at different time points during the memory process. Blocking PKA anchoring to AKAPs resulted in an impairment of fear memory consolidation. Moreover, disrupted PKA anchoring promoted contextual fear extinction in the mouse hippocampus. We conclude that the temporal and spatial compartmentalization of hippocampal PKA signaling pathways, as achieved by anchoring of PKA to AKAPs, is specifically instrumental in long-term contextual fear memory consolidation and extinction, but not in acquisition and retrieval.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalNeurobiology of Learning and Memory
Volume90
Issue number1
DOIs
Publication statusPublished - Jul 1 2008

Keywords

  • A-kinase anchoring protein
  • Extinction
  • Fear conditioning
  • Hippocampus
  • Ht31
  • Learning
  • Memory
  • Mouse
  • SuperAKAP-IS

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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