The University of Tokyo, Bunkyo-ku, Japan.
Genes Cells. 2010 Jun;15(7):737-47. doi: 10.1111/j.1365-2443.2010.01411.x. Epub 2010 Jun 10.
Actin reorganization in dendritic spines is hypothesized to underlie neuronal plasticity. Actin-related proteins, therefore, might serve as useful markers of plastic changes in dendritic spines. Here, we utilized memory deficits induced by fimbria-fornix transection (FFT) in rats as a dementia model to screen candidate memory-associated molecules by using a two-dimensional gel method. Comparison of protein profiles between the transected and control sides of hippocampi after unilateral FFT revealed a reduction in the F-actin capping protein (CapZ) signal on the FFT side. Subsequent immunostaining of brain sections and cultured hippocampal neurons revealed that CapZ localized in dendritic spines and the signal intensity in each spine varied widely. The CapZ content decreased after suppression of neuronal firing by tetrodotoxin treatment in cultured neurons, indicating rapid and activity-dependent regulation of CapZ accumulation in spines. To test input specificity of CapZ accumulation in vivo, we delivered high-frequency stimuli to the medial perforant path unilaterally in awake rats. This path selectively inputs to the middle molecular layer of the dentate gyrus, where CapZ immunoreactivity increased. We conclude that activity-dependent, synapse-specific regulation of CapZ redistribution might be important in both maintenance and remodeling of synaptic connections in neurons receiving specific spatial and temporal patterns of inputs.
肌动蛋白在树突棘中的重排被假设为神经元可塑性的基础。因此，肌动蛋白相关蛋白可能作为树突棘中塑性变化的有用标志物。在这里，我们利用大鼠穹窿伞横断（FFT）引起的记忆缺陷作为痴呆模型，通过二维凝胶方法筛选候选记忆相关分子。单侧 FFT 后海马体切断侧和对照侧的蛋白质图谱比较显示， F-肌动蛋白封端蛋白（CapZ）信号在 FFT 侧减少。随后对脑切片和培养的海马神经元进行免疫染色显示，CapZ 定位于树突棘中，每个棘突的信号强度差异很大。在培养神经元中用河豚毒素抑制神经元放电后，CapZ 含量下降，表明 CapZ 在棘突中的积累是快速的且依赖于活动的调节。为了测试 CapZ 在体内积累的输入特异性，我们在清醒大鼠中单侧给予高频刺激到内侧穿通路径。该路径选择性地输入到齿状回的中间分子层，其中 CapZ 免疫反应性增加。我们的结论是，CapZ 重分布的活动依赖性、突触特异性调节可能对接受特定空间和时间输入模式的神经元中突触连接的维持和重塑很重要。
