Changes in synaptic morphology accompany actin signaling during LTP
Changes in synaptic morphology accompany actin signaling during LTP
复制标题
DOI：
10.1523/jneurosci.0164-07.2007
复制
发表时间：
2007-05-16
影响因子：
5.3
通讯作者：
Lynch, Gary
中科院分区：
文献类型：
--
作者：
Chen, Lulu Y.;Rex, Christopher S.;Lynch, Gary
长期增强（LTP）的稳定通常被认为与突触形态的改变和脊柱细胞骨架的重组有关。在这里，我们测试了是否如该假设所预测的那样，通过θ -burst刺激诱导LTP激活了肌动蛋白调节途径并改变了同一树突棘内的突触形态。TBS使含有磷酸化(p) p21活化激酶（PAK）或其下游靶蛋白cofilin的棘数增加数倍；后者调节肌动蛋白丝的组装。PAK/cofilin磷酸化蛋白在tbs后2 min升高，30 s不升高，7 min达到峰值，随后下降。突触后密度蛋白PSD95的双重免疫染色显示，高pPAK或pCofilin水平的棘比邻近的棘具有更大的突触（+60-70%）和更正常的大小频率分布。基于这些结果和对突触样物体形状变化的模拟，我们提出，θ波刺激显著增加脊椎进入以大卵形突触为特征的状态的可能性，这种形态对LTP的表达和后来的稳定很重要。
Stabilization of long-term potentiation ( LTP) is commonly proposed to involve changes in synaptic morphology and reorganization of the spine cytoskeleton. Here we tested whether, as predicted from this hypothesis, induction of LTP by theta-burst stimulation activates an actin regulatory pathway and alters synapse morphology within the same dendritic spines. TBS increased several fold the numbers of spines containing phosphorylated ( p) p21-activated kinase ( PAK) or its downstream target cofilin; the latter regulates actin filament assembly. The PAK/cofilin phosphoproteins were increased at 2 min but not 30 s post-TBS, peaked at 7 min, and then declined. Double immunostaining for the postsynaptic density protein PSD95 revealed that spines with high pPAK or pCofilin levels had larger synapses ( +60-70%) with a more normal size frequency distribution than did neighboring spines. Based on these results and simulations of shape changes to synapse-like objects, we propose that theta stimulation markedly increases the probability that a spine will enter a state characterized by a large, ovoid synapse and that this morphology is important for expression and later stabilization of LTP.