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

• Published in: Neurobiology of learning and memory 2014-11, Vol.115, p.78-85
• Main Authors: Tedesco, Vincenzo, Roquet, Rheall F., DeMis, John, Chiamulera, Cristiano, Monfils, Marie-H.
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Amygdala; Animals; Basolateral Nuclear Complex - chemistry; Basolateral Nuclear Complex - physiology; Behavioral psychophysiology; Biological and medical sciences; Conditioning, Classical - physiology; Early Growth Response Protein 1 - analysis; Early Growth Response Protein 1 - biosynthesis; Early Growth Response Protein 1 - physiology; Extinction; Extinction, Psychological - physiology; Fear - physiology; Fear conditioning; Fundamental and applied biological sciences. Psychology; Male; Memory; Mental Recall - physiology; Neurobiology; Phosphorylation; Prefrontal cortex; Prefrontal Cortex - chemistry; Prefrontal Cortex - physiology; Protein expression; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats, Sprague-Dawley; Reconsolidation; Retrieval; Ribosomal Protein S6 - analysis; Ribosomal Protein S6 - biosynthesis; Ribosomal Protein S6 - physiology; rpS6P; Zif268
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2014.08.015

•Retrieval and Ret–Ext, but not extinction alone, increase Zif268 expression in prefrontal cortex and lateral amygdala.•Ret–Ext, but not retrieval or extinction alone, increase the expression of rpS6P in prefrontal cortex and lateral amygdala.•Extinction, applied after retrieval, is incorporated in a memory reconsolidation process. 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