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Learning and Long-term Memory

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

Up-regulation of CREB activity in forebrain enhances working-like memory and increases in spine density

  • P2-255
  • 芹田 龍郎 / Tatsurou Serita:1 福島 穂高 / Hotaka Fukushima:1,2 喜田 聡 / Satoshi Kida:1,2 
  • 1:東京農業大学 / Dept. of Bioscience, Tokyo Univ. of Agriculture 2:JST、CREST / JST, CREST 

Transcription factor CREB plays in essential roles in formation of long-term memory (LTM). To understand roles of CREB in learning and memory, we have examined effects of gain-of-CREB function on memory formation by generating transgenic mice expressing a constitutively active CREB mutant (CREB DIEDML) in the forebrain. Interestingly, these transgenic mice displayed enhancement of not only LTM but also short-term memory (STM), suggesting that CREB positively regulates both LTM and STM (Suzuki et al, 2011). These findings raise the possibility that CREB plays critical roles in learning processes. To ask this, we first examined the ability of temporal association learning and spatial working memory in DIEDML mice. In the trace fear conditioning task, mice learn an association between the conditioned stimulus (CS; tone) and the unconditioned stimulus (US; footshock) separated by the trace interval. During the training that consists of 8 CS-trace-US-intertrial interval, mice were assessed freezing responses during each trace interval. DIEDML mice learned trace fear conditioning significantly faster and better compared to wild-type (WT) mice. We next performed working memory version of Morris water maze task in which mice were given training with 4 trials (trial 1-4) per day and the position of platform was changed every day. DIEDML mice showed significantly more decreases in escape latencies to the platform at the trial 2-4 compared to WT mice although these mutant mice displayed normal escape latency at the trial 1. These results indicated that DIEDML mice showed enhancement of working memory. Thus our results suggest that up-regulation of CREB activity improves working-like memories. Furthermore, morphological analysis of dendritic spine in hippocampus revealed that DIEDML mice showed significant increase in spine density compared to WT mice.

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