Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation.
Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation.
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AMPA 受体递送至突触周围位点先于长时程增强的完全表达。
DOI：
10.1073/pnas.0802978105
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发表时间：
2008
影响因子：
11.1
通讯作者：
Zhou,Qiang
中科院分区：
文献类型：
--
作者：
Yang,Yunlei;Wang,Xiao-Bin;Frerking,Matthew;Zhou,Qiang
AMPA亚型谷氨酸受体（AMPAR）从细胞内区室到突触的运输被认为是长时程增强（LTP）表达的主要机制，LTP是学习和记忆的细胞底物。然而，目前尚不清楚在LTP期间发生的AMPAR运输是由于AMPAR直接靶向插入突触还是递送到突触外位点随后易位到突触中。在这里，我们提供了直接的生理证据表明，由θ-爆发配对和强直刺激方案引起的LTP导致AMPAR快速传递到突触周围部位。突触周AMPAR通常不检测突触释放的谷氨酸，但当神经胶质谷氨酸转运体EAAT 1被抑制时可以检测到。在LTP完全表达之前，但之后，可以在该突触周围位点检测到AMPAR。突触周AMPAR的出现需要突触后胞吐、PKA信号和AMPAR GluR 1亚基的C-末端区域，而不是肌动蛋白聚合。LTP诱导后的肌动蛋白聚合需要在其出现后将AMPAR保留在突触周围位点。LTP诱导后不久给予的低频刺激导致突触周围AMPAR的活性依赖性去除，并抑制LTP的后续表达。这些结果表明，AMPAR被迅速贩运到突触周围的网站后不久，LTP的诱导，并表明，传递和维护突触周围的AMPAR可能作为一个检查点的LTP的表达。
Trafficking of AMPA subtype glutamate receptors (AMPARs) from intracellular compartments to synapses is thought to be a major mechanism underlying the expression of long-term potentiation (LTP), a cellular substrate for learning and memory. However, it remains unclear whether the AMPAR trafficking that takes place during LTP is due to a targeted insertion of AMPARs directly into the synapse or delivery to extrasynaptic sites followed by translocation into the synapse. Here, we provide direct physiological evidence that LTP induced by a theta-burst pairing and tetanic stimulation protocols causes the rapid delivery of AMPARs to a perisynaptic site. Perisynaptic AMPARs do not normally detect synaptically released glutamate but can do so when the glial glutamate transporter EAAT1 is inhibited. AMPARs can be detected at this perisynaptic site before, but not after, the full expression of LTP. The appearance of perisynaptic AMPARs requires postsynaptic exocytosis, PKA signaling, and the C-terminal region of GluR1 subunit of AMPARs but not actin polymerization. Actin polymerization after LTP induction is required to retain AMPARs at the perisynaptic site after their appearance. Low-frequency stimulation given shortly after LTP induction leads to activity-dependent removal of perisynaptic AMPARs and suppresses the subsequent expression of LTP. These results demonstrate that AMPARs are rapidly trafficked to perisynaptic sites shortly after LTP induction and suggest that the delivery and maintenance of perisynaptic AMPARs may serve as a checkpoint in the expression of LTP.