期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 42, 页码 18173-18178出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1006546107
关键词
plasticity; seizure; AMPA receptors
资金
- National Institute of Neurological Disorders and Stroke [2R01 NS0390746, 2R01 NS045191]
- National Institute on Aging [2P01 AG022074]
- Keck Foundation [NS29709, IDDRC HD024064]
- National Institutes of Health/National Institute of General Medical Sciences University of California at San Francisco
- National Institutes of Health [C06 RR018928]
Long-term memory relies on modulation of synaptic connections in response to experience. This plasticity involves trafficking of AMPA receptors (AMPAR) and alteration of spine morphology. Arc, a gene induced by synaptic activity, mediates the endocytosis of AMPA receptors and is required for both long-term and homeostatic plasticity. We found that Arc increases spine density and regulates spine morphology by increasing the proportion of thin spines. Furthermore, Arc specifically reduces surface GluR1 internalization at thin spines, and Arc mutants that fail to facilitate AMPAR endocytosis do not increase the proportion of thin spines, suggesting that Arc-mediated AMPAR endocytosis facilitates alterations in spine morphology. Thus, by linking spine morphology with AMPAR endocytosis, Arc balances synaptic downscaling with increased structural plasticity. Supporting this, loss of Arc in vivo leads to a significant decrease in the proportion of thin spines and an epileptic-like network hyperexcitability.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据