Distinct roles of hippocampal de novo protein synthesis and actin rearrangement in extinction of contextual fear.
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.
Fischer
André
A
Laboratory on Cell Biological Mechanisms of Memory, Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, 37075 Goettingen, Germany.
Sananbenesi
Farahnaz
F
Schrick
Christina
C
Spiess
Joachim
J
Radulovic
Jelena
J
D000161:Acoustic Stimulation; D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003214:Conditioning, Classical / Q000502:physiology; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011500:Protein Synthesis Inhibitors; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; D000841:Anisomycin; C037067:latrunculin A