2014年10月
Region-Specific Activation of CRTC1-CREB Signaling Mediates Long-Term Fear Memory
NEURON
- 巻
- 84
- 号
- 1
- 開始ページ
- 92
- 終了ページ
- 106
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.neuron.2014.08.049
- 出版者・発行元
- CELL PRESS
CREB is a pivotal mediator of activity-regulated gene transcription that underlies memory formation and allocation. The contribution of a key CREB cofactor, CREB-regulated transcription coactivator 1 (CRTC1), has, however, remained elusive. Here we show that several constitutive kinase pathways and an activity-regulated phosphatase, calcineurin, converge to determine the nucleocytoplasmic shuttling of CRTC1. This, in turn, triggered an activity-dependent association of CRTC1 with CREB-dependent regulatory elements found on IEG promoters. Forced expression of nuclear CRTC1 in hippocampal neurons activated CREB-dependent transcription, and was sufficient to enhance contextual fear memory. Surprisingly, during contextual fear conditioning, we found evidence of nuclear recruitment of endogenous CRTC1 only in the basolateral amygdala, and not in the hippocampus. Consistently, CRTC1 knockdown in the amygdala, but not in the hippocampus, significantly attenuated fear memory. Thus, CRTC1 has a wide impact on CREB-dependent memory processes, but fine-tunes CREB output in a region-specific manner.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.neuron.2014.08.049
- ISSN : 0896-6273
- eISSN : 1097-4199
- PubMed ID : 25277455
- Web of Science ID : WOS:000342502800013