GluR1 links structural and functional plasticity at excitatory synapses
GluR1 links structural and functional plasticity at excitatory synapses
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DOI：
10.1523/jneurosci.3503-07.2007
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发表时间：
2007-12-12
影响因子：
5.3
通讯作者：
Malinow, Roberto
中科院分区：
文献类型：
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作者：
Kopec, Charles D.;Real, Eleonore;Malinow, Roberto
长时程增强（LTP）是一种学习和记忆的细胞模型，可以增强突触功能并增加相关树突棘的大小。已知 AMPA 受体的突触插入在介导 LTP 期间突触强度的增加中发挥重要作用，而 AMPA 受体运输在结构变化中的作用仍未被探索。在这里，我们研究了细胞如何在 LTP 期间维持脊柱大小和突触强度之间的相关性。我们发现细胞利用了一种优雅的解决方案，将这两个过程连接到一个分子：AMPA 型谷氨酸受体亚基 1 (GluR1)。无论是在海马切片培养物中还是在体内，GluR1 的突触插入都是允许脊柱大小稳定增加所必需的。 GluR1 的突触插入不足以驱动结构可塑性。尽管 GluR1 的离子通道功能对于 LTP 的表达至关重要，但 LTP 驱动的脊柱尺寸增强并不需要 GluR1 的离子通道功能。值得注意的是，在 LTP 刺激后，GluR1 的重组胞质 C 末端片段（C 尾）被驱动至突触后密度，即使内源性 GluR1 的突触后胞吐作用被阻断，这种分离的 GluR1 C 尾的突触掺入也足以允许脊柱增大。我们得出的结论是，在可塑性过程中，GluR1 的突触插入具有两个功能：通过其配体门控离子通道增加突触强度的既定作用，以及通过其 C 末端的结构稳定作用（允许增加脊柱大小）的新作用。
Long-term potentiation (LTP), a cellular model of learning and memory, produces both an enhancement of synaptic function and an increase in the size of the associated dendritic spine. Synaptic insertion of AMPA receptors is known to play an important role in mediating the increase in synaptic strength during LTP, whereas the role of AMPA receptor trafficking in structural changes remains unexplored. Here, we examine how the cell maintains the correlation between spine size and synapse strength during LTP. We found that cells exploit an elegant solution by linking both processes to a single molecule: the AMPA-type glutamate receptor subunit 1 (GluR1). Synaptic insertion of GluR1 is required to permit a stable increase in spine size, both in hippocampal slice cultures and in vivo. Synaptic insertion of GluR1 is not sufficient to drive structural plasticity. Although crucial to the expression of LTP, the ion channel function of GluR1 is not required for the LTP-driven spine size enhancement. Remarkably, a recombinant cytosolic C-terminal fragment (C-tail) of GluR1 is driven to the postsynaptic density after an LTP stimulus, and the synaptic incorporation of this isolated GluR1 C-tail is sufficient to permit spine enlargement even when postsynaptic exocytosis of endogenous GluR1 is blocked. We conclude that during plasticity, synaptic insertion of GluR1 has two functions: the established role of increasing synaptic strength via its ligand-gated ion channel, and a novel role through the structurally stabilizing effect of its C terminus that permits an increase in spine size.