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Learning and Long-term Memory

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Time-dependent regulation of memory retrieval by forebrain circadian clock

  • P1-279
  • 長谷川 俊介 / Shunsuke Hasegawa:1,2 細田 浩司 / Hiroshi Hosoda:1 張 悦 / Yue Zhang:1 太田 美穂 / Miho Ohta:1 谷水 俊之 / Toshiyuki Tanimizu:1 Frankland Paul W / Paul W Frankland:3 Josselyn Sheena A / Sheena A Josselyn:3 喜田 聡 / Satoshi Kida:1,2 
  • 1:東京農大応用生物バイオ / Dept. Biosci., Tokyo Univ. of Agric., Tokyo, Japan 2:科学技術振興機構・CREST / JST, CREST, Tokyo, Japan 3:トロント大学 / Univ. of Toronto, Toronto, Canada 

Cognitive performance in people varies according to time-of-day, with memory retrieval declining in the later afternoon-early evening. Here we show that mice exhibit a similar time-of-day regulation of memory retrieval that correlates with low forebrain levels of a key circadian transcription factor, BMAL1. To test whether forebrain clock regulates the efficiency of memory retrieval, we inducibly expressed a dominant negative BMAL1 (BMAL1 R91A; dnBMAL1; Hosoda et al, 2004) exclusively in the forebrain. Biochemical analyses showed that dnBMAL1 mice exhibit disruptions of circadian expression cycle of BMAL1/CLOCK-target genes in the hippocampus, but not in the SCN. In addition, dnBMAL1 mice displayed normal circadian rhythms at the behavioral level. These results indicated that inhibition of BMAL1 activity disrupts forebrain circadian clock without affecting behavioral circadian rhythms. Behavioral analyses using social recognition task showed that these mutant mice exhibited impairments in memory retrieval tested around ZT10 in a dnBMAL1 expression-dependent manner, while these mutant mice displayed normal memory retrieval tested at ZT4, 16, or 22 under strong training conditions. Furthermore, dnBMAL1 mice showed disability of memory retrieval even at ZT4 under weak training conditions. Similar impairments of memory retrieval in these mutant mice were also observed in constant dark (CT) conditions. Importantly, even WT mice showed impairments in memory retrieval at ZT10 under the weak training condition but showed normal memory retrieval under strong training conditions. Taken together, these findings indicate that forebrain circadian clock regulates memory retrieval in a circadian time-dependent manner.

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