title: Extinction, applied after retrieval of auditory fear memory, selectively increases zinc-finger protein 268 and phosphorylated ribosomal protein S6 expression in prefrontal cortex and lateral amygdala.
abstract: Retrieval of consolidated memories induces a labile phase during which memory can be disrupted or updated through a reconsolidation process. A central component of behavioral updating during reconsolidation using a retrieval-extinction manipulation (Ret+Ext) is the synaptic removal of a calcium-permeable-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (CP-AMPARs) in the lateral amygdala-a metabotropic GluR1 receptor (mGluR1) dependent mechanism. In the present study, we investigate the effect of Ret+Ext on the expression of molecular markers that could play a role in the reconsolidation process. Specifically, we tested the effects of Ret+Ext on the global expression of zinc-finger 268 protein (Zif268), a marker previously found to be implicated in memory reconsolidation, to confirm its occurrence after retrieval (Ret) and Ret+Ext. We also evaluated the global expression of phosphorylated ribosomal protein S6 (rpS6P), here proposed as a marker of the mGluR1-mediated memory process induced by Ret+Ext. The expression of both markers (zif268, rpS6P) was assessed by immunolocalization in prelimbic cortex (PRL), infralimbic cortex (IL), ventral subdivision of the lateral amygdala (LA) and hippocampus CA1 (CA1) in fear-conditioned rats. Our results showed that retrieval and Ret+Ext, but not extinction alone, increased Zif268 expression in prefrontal cortex and lateral amygdala. Ret+Ext, but not retrieval, retrieval followed by context exposure or extinction alone, increased the expression of rpS6P in prefrontal cortex and LA. In summary, (i) Zif268 increased after retrieval confirming that reconsolidation is engaged in our conditions, (ii) Zif268 increased after Ret+Ext confirming that it does not simply reflect an extinction or reconsolidation disruption (Zif268 level of expression should be lower in both cases) and (iii) rpS6P increased after Ret+Ext, but not after extinction, suggesting, as expected, a potential mGluR1 mediated molecular mechanism specific for Ret+Ext. Together with the Zif268 increase, our results suggest that the Ret+Ext induced memory process is more similar to reconsolidation updating than extinction facilitation.
authors.affiliation: Department of Public Health & Community Medicine, University of Verona, 37134 Verona, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tedesco
authors.affiliation: Department of Psychology, University of Texas at Austin, 78712-0187 Austin, TX, USA.
authors.forename: Rheall F
authors.initials: RF
authors.lastname: Roquet
authors.affiliation: Department of Psychology, University of Texas at Austin, 78712-0187 Austin, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: DeMis
authors.affiliation: Department of Public Health & Community Medicine, University of Verona, 37134 Verona, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiamulera
authors.affiliation: Department of Psychology, University of Texas at Austin, 78712-0187 Austin, TX, USA. Electronic address: marie.monfils@utexas.edu.
authors.forename: Marie-H
authors.initials: MH
authors.lastname: Monfils
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D066272:Basolateral Nuclear Complex / Q000737:chemistry / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000737:chemistry / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D038601:Ribosomal Protein S6 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D038601:Ribosomal Protein S6
keywords: Amygdala; Extinction; Fear conditioning; Prefrontal cortex; Reconsolidation; Retrieval; Zif268; rpS6P