Kopec Charles D, Real Eleonore, Kessels Helmut W, Malinow Roberto
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
J Neurosci. 2007 Dec 12;27(50):13706-18. doi: 10.1523/JNEUROSCI.3503-07.2007.
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.
长时程增强（LTP）是学习和记忆的一种细胞模型，它既能增强突触功能，又能增大相关树突棘的尺寸。已知AMPA受体的突触插入在介导LTP期间突触强度增加中起重要作用，而AMPA受体转运在结构变化中的作用仍未得到探索。在这里，我们研究细胞在LTP期间如何维持树突棘大小与突触强度之间的相关性。我们发现细胞通过将这两个过程与单个分子联系起来，找到了一个巧妙的解决方案：AMPA型谷氨酸受体亚基1（GluR1）。无论是在海马脑片培养物中还是在体内，GluR1的突触插入都是树突棘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。虽然对LTP的表达至关重要，但LTP驱动的树突棘大小增强并不需要GluR1的离子通道功能。值得注意的是，LTP刺激后，GluR1的重组胞质C末端片段（C尾）被驱动到突触后致密区，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使树突棘增大。我们得出结论，在可塑性过程中，GluR1的突触插入有两个功能：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树突棘大小增加的新作用。
