Department of Biology, National Center for Behavioral Genomics, Rosenstiel Basic Medical Sciences Research Center, and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
J Neurosci. 2014 Jan 8;34(2):392-407. doi: 10.1523/JNEUROSCI.1328-13.2014.
A key feature of the CNS is structural plasticity, the ability of neurons to alter their morphology and connectivity in response to sensory experience and other changes in the environment. How this structural plasticity is achieved at the molecular level is not well understood. We provide evidence that changes in sensory experience simultaneously trigger multiple signaling pathways that either promote or restrict growth of the dendritic arbor; structural plasticity is achieved through a balance of these opposing signals. Specifically, we have uncovered a novel, activity-dependent signaling pathway that restricts dendritic arborization. We demonstrate that the GTPase Rem2 is regulated at the transcriptional level by calcium influx through L-VGCCs and inhibits dendritic arborization in cultured rat cortical neurons and in the Xenopus laevis tadpole visual system. Thus, our results demonstrate that changes in neuronal activity initiate competing signaling pathways that positively and negatively regulate the growth of the dendritic arbor. It is the balance of these opposing signals that leads to proper dendritic morphology.
中枢神经系统的一个关键特征是结构可塑性，即神经元能够根据感觉经验和环境中的其他变化改变其形态和连接。这种结构可塑性在分子水平上是如何实现的还不是很清楚。我们提供的证据表明，感觉经验的变化同时触发了多种信号通路，这些信号通路要么促进，要么限制树突棘的生长；结构可塑性是通过这些相反信号的平衡来实现的。具体来说，我们发现了一种新的、活性依赖的信号通路，它限制树突棘的分支。我们证明，GTPase Rem2 通过 L-VGCC 介导的钙内流在转录水平受到调控，并抑制培养的大鼠皮质神经元和非洲爪蟾蝌蚪视觉系统中的树突棘分支。因此，我们的结果表明，神经元活动的变化引发了竞争的信号通路，这些信号通路正向和负向调节树突棘的生长。正是这些相反信号的平衡导致了适当的树突形态。
