AMPA受体
生物
长期抑郁
内化
细胞生物学
长时程增强
突触后电位
谷氨酸受体
半胱氨酸蛋白酶
NMDA受体
受体
海马结构
神经科学
程序性细胞死亡
细胞凋亡
生物化学
作者
Zheng Li,Jihoon Jo,Jie–Min Jia,S.-C.B. Lo,Daniel J. Whitcomb,Ji‐Hyun Song,Kwangwook Cho,Morgan Sheng
出处
期刊:Cell
[Elsevier]
日期:2010-05-01
卷期号:141 (5): 859-871
被引量:467
标识
DOI:10.1016/j.cell.2010.03.053
摘要
NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD.
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