PT - JOURNAL ARTICLE AU - André Fischer AU - Farahnaz Sananbenesi AU - Christina Schrick AU - Joachim Spiess AU - Jelena Radulovic TI - Distinct Roles of Hippocampal <em>De Novo</em> Protein Synthesis and Actin Rearrangement in Extinction of Contextual Fear AID - 10.1523/JNEUROSCI.5112-03.2004 DP - 2004 Feb 25 TA - The Journal of Neuroscience PG - 1962--1966 VI - 24 IP - 8 4099 - http://www.jneurosci.org/content/24/8/1962.short 4100 - http://www.jneurosci.org/content/24/8/1962.full SO - J. Neurosci.2004 Feb 25; 24 AB - 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.