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Learning and Long-term Memory

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Retinoic acid signaling pathway positively regulates hippocampus-dependent memory formation

  • P3-218
  • 海老原 てい / Tei Ebihara:1 篠澤 貴寛 / Takahiro SHINOZAWA:1 野本 真順 / Masanori NOMOTO:1 武田 陽平 / Yohei TAKEDA:1 内田 周作 / Shusaku UCHIDA:1 喜田 聡 / Satoshi KIDA:1,2 
  • 1:東京農大院・農・バイオ / Dept. of Bioscience, Tokyo Univ. of Agriculture 2:科学技術振興機構CREST / CREST・JST 

Retinoic acid (RA), a metabolite of Vitamin A, acts as a specific ligand for retinoic acid receptors (RARs) and retinoid X receptor (RXR) and regulates various biological phenomena through transcriptional regulation. Importantly, RARs highly and ubiquitously express in brain. Our previous studies have shown that genetic inhibition of RA signaling pathways by expressing a dominant negative mutant of RAR in the forebrain impairs hippocampal LTP and hippocampus-dependent memories, indicating that RARs play a critical role in hippocampal synaptic plasticity and memory. In this study, we examined effects of gain-of-RAR functions on hippocampus-dependent learning and memory. Consistent with our previous studies, mice infused RAR-alpha antagonist (Ro41-5253) into the hippocampus 4 hours before training displayed impairments in the formation of spatial, social recognition and fear memories. In contrast, mice infused RARs agonist (All-trans retinoic acid; ATRA) displayed improvements of these memories. We next generated conditional mutant mice that enable to induce forebrain-specific expression of wild-type RAR-alpha (WT-RAR mice). These WT-RAR mice showed up-regulation of RARs-target gene RAR-beta in the hippocampus following the intraperitoneal injection of ATRA, indicating that WT-RAR mice showed stronger activation of RA-signaling pathway than WT mice. More importantly, WT-RAR mice displayed enhancements of hippocampus-dependent memories only when they received intraperitoneal injection of ATRA 4 hours before training. Taken together, our results indicate that up-regulation of RA signaling pathway in the hippocampus enhances the formation of hippocampus-dependent memory, suggesting that RA positively regulates memory formation.

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