Distinct Roles of Hippocampal De Novo Protein Synthesis and Actin Rearrangement in Extinction of Contextual Fear

André Fischer, Farahnaz Sananbenesi, Christina Schrick, Joachim Spiess, Jelena Radulovic*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

It is believed that de novo protein synthesis is fundamentally linked to synaptic changes in neuronal circuits involved in acquisition and extinction of conditioned responses. Recent studies show that neuronal plasticity may be also altered by cytoskeletal rearrangement independently of protein synthesis. We investigated the role of these processes in the hippocampus during acquisition and extinction of context-dependent conditioned fear in mice. Intrahippocampal injections of the protein synthesis inhibitors anisomycin and puromycin, or of the actin rearrangement inhibitors cytochalasin D and latrunculin A, prevented the acquisition of context-dependent fear. Unexpectedly, anisomycin and puromycin enhanced extinction without erasing the fear memory. In contrast, cytochalasin D and latrunculin A prevented extinction of context-dependent freezing. On the basis of these findings, it is suggested that certain hippocampal mechanisms mediating extinction of conditioned contextual fear are inhibited by protein synthesis and involve actin rearrangement. Such mechanisms might predominantly elicit modifications of hippocampal circuits that store the conditioning memory.

Original languageEnglish (US)
Pages (from-to)1962-1966
Number of pages5
JournalJournal of Neuroscience
Volume24
Issue number8
DOIs
StatePublished - Feb 25 2004

Keywords

  • Actin rearrangement
  • Extinction
  • Fear conditioning
  • Hippocampus
  • Mice
  • Protein synthesis

ASJC Scopus subject areas

  • Neuroscience(all)

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