演題番号 : P1-m16
金 亮 / Ryang Kim:1,2 Karim Nader:3 喜田 聡 / Satoshi Kida:1,2
1:東京農大院・農・バイオ / Dep. Bioscience, Tokyo Univ. of Agriculture, Tokyo, Japan 2:CREST, JST 3:マギル大・心理 / Dept. Psychology, McGill Univ., Montreal, Canada
Retrieval of conditioned fear memory by re-exposure to conditioned stimulus (CS) initiates reconsolidation or extinction. We previously found that reconsolidation and extinction of contextual fear memory requires activation of CREB through phosphorylation at Serine 133 in the hippocampus/amygdala or amygdala/medial prefrontal cortex, respectively (Kida et al, 2002; Mamiya et al, 2009). In addition, we observed that short re-exposure (3min) to CS inducing reconsolidation increase in CREB phosphorylation in hippocampus, whereas the prolonged re-exposure (30min) inducing extinction prevented this CREB phosphorylation. These observations suggest that regulation of phosphorylation and dephosphorylation of CREB by CREB-kinase and phosphatase, respectively, plays critical roles in the determination for the fate of fear memory; reconsolidation or extinction. In this study, we tried to understand roles of calcineurin, also named Protein Phosphatase 2B (PP2B), in reconsolidation and extinction of contextual of fear memory. Infusion of calcineurin inhibitor FK506 into hippocampus after 3min re-exposure to CS prevented the disruption of reactivated memory by protein synthesis inhibitor anisomycin (ANI). This prevention of amnesic ANI-effect by FK506 was observed when FK506 was infused into amygdala. In addition, hippocampal FK506-infusion just before 30min re-exposure to the CS impaired the acquisition of extinction. These data suggest that activation of hippocampal and amygdaloid calcineurin plays essential roles in destabilization and extinction of reactivated contextual fear memory.