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Gene Regulation and Epigenetics

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Light stimuli alter the activity status of CREB and CRTC1 in the primary visual cortex of adult marmosets

  • P3-037
  • 仲神 友貴 / Yuki Nakagami:1 渡我部 昭哉 / AKIYA WATAKABE:1 竹森 洋 / HIROSHI TAKEMORI:2 山森 哲雄 / TETSUO YAMAMORI:1 
  • 1:基生研 脳生物学 / Div Brain Biol, Nat Inst Basic Biol, Aichi, Japan 2:医薬基盤研 代謝疾患関連タンパク探索プロジェクト / Lab Cell Sig & Metab, Nat Inst Biomed Innov, Osaka, Japan 

Sensory inputs induce the expression of various immediate early genes (IEGs, i.e. c-FOS) in brain. We previously reported that light stimuli induced dynamic changes of IEGs expression in the primary visual cortex (V1) of adult marmosets. Each IEG exhibited various time course of gene expression unique to each layer within short term from stimulus onset, suggesting that the regulatory mechanism of gene expression is different layer by layer. To address the mechanism of light-induced transcription in adult marmoset V1, we focused in this study on cAMP-response element-binding protein (CREB), known as a key regulator of activity-dependent gene expression. To investigate the effect of retinal input on IEGs expression in V1, we monocularly blocked retinal activity by injection of TTX, kept the animals in darkness for 24-48 hours, then exposed to light for 0, 7, 24, 140, and 240 minutes. We analyzed the changes in activity state of CREB and CREB regulated transcription coactivator 1 (CRTC1) by immunohistochemistry: phosphorylation and nuclear localization, respectively. We observed that CREB was already phosphorylated at ser133 in layer IVCβ without light stimulation. To our surprise, phosphorylation of CREB at ser133 transiently decreased in the input-received ocular dominance columns of layer IVCβ, where IEGs increased, after 24 minutes of light stimulation, which later recovered to the original level. At the same time, CRTC1-immunoreactivity increased in the nucleus 7 and 24 min after light stimulation and then cleared from the nucleus. At this time point, mRNA expression of salt-inducible kinase 1 (SIK1), which is known to be down-stream of CRTC1, was also observed in layer IVCβ of V1. These results suggest that CREB and CRTC1 contribute to regulations of light-stimulation-induced transcription of IEGs in layer IVCβ of marmoset V1.

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