Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines

Activity-Dependent Dynamic Microtubule Invasion of Dendritic Spines
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DOI:
10.1523/jneurosci.3074-08.2008
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发表时间:
2008-12-03
影响因子:
5.3
通讯作者:
Dent, Erik W.
Dent, Erik W.
中科院分区:
医学1区
文献类型:
--
作者:
Hu, Xindao;Viesselmann, Chris;Dent, Erik W.

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树突棘是与兴奋性海马和皮质神经元上的突触前轴突接触的主要部位。在发育和可塑性过程中,棘的结构发生了显著的变化,直接影响神经元之间的功能性通讯。阐明诱导这些结构变化的细胞骨架事件是理解突触生物学的基础。肌动蛋白在脊椎细胞骨架中起着核心作用,但微管在脊椎功能中的作用研究很少。虽然微管在整个树突中运输预定用于棘的物质方面具有突出的作用,但它们不被认为直接影响棘的结构或功能。使用全内反射荧光显微镜,我们发现,微管迅速侵入成熟的中枢神经系统神经元的树突状突起(在体外长达63天),偶尔与显着的变化,在脊柱形态的形式,短暂的脊柱头突起(tSHP)。两个微管可以同时占据棘,并且微管靶向可以从近端和远端树突发生。一小部分spine是一次定位的,所有的定位事件都是短暂的,平均只有几分钟。然而,随着时间的推移,树突上的许多刺被微管靶向。重要的是,我们发现,增加神经元的活动增加了微管入侵的棘的数量和这些入侵的持续时间。这项研究提供了新的见解,在成熟的中枢神经系统神经元的神经细胞骨架的动力学,并表明,微管在脊柱的形态和功能中发挥着重要的,直接的作用。
Dendritic spines are the primary sites of contact with presynaptic axons on excitatory hippocampal and cortical neurons. During development and plasticity spines undergo marked changes in structure that directly affect the functional communication between neurons. Elucidating the cytoskeletal events that induce these structural changes is fundamental to understanding synaptic biology. Actin plays a central role in the spine cytoskeleton, however the role of microtubules in spine function has been studied little. Although microtubules have a prominent role in transporting material throughout the dendrite that is destined for spines, they are not thought to directly influence spine structure or function. Using total internal reflectance fluorescent microscopy we discovered that microtubules rapidly invade dendritic protrusions of mature CNS neurons ( up to 63 d in vitro), occasionally being associated with marked changes in spine morphology in the form of transient spine head protrusions (tSHPs). Two microtubules can occupy a spine simultaneously and microtubule targeting can occur from both the proximal and distal dendrite. A small percentage of spines are targeted at a time and all targeting events are transient, averaging only a few minutes. Nevertheless, over time many spines on a dendrite are targeted by microtubules. Importantly, we show that increasing neuronal activity enhances both the number of spines invaded by microtubules and the duration of these invasions. This study provides new insight into the dynamics of the neuronal cytoskeleton in mature CNS neurons and suggests that microtubules play an important, direct role in spine morphology and function.