Bagal Ashish A, Kao Joseph P Y, Tang Cha-Min, Thompson Scott M
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14434-9. doi: 10.1073/pnas.0501956102. Epub 2005 Sep 26.
Long-term increases in the strength of excitatory transmission at Schaffer collateral-CA1 cell synapses of the hippocampus require the insertion of new alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) into the synapse, but the kinetics of this process are not well established. Using microphotolysis of caged glutamate to activate receptors at single dendritic spines in hippocampal CA1 cells, we report the long-lasting potentiation of AMPAR-mediated currents with only a single pairing of photoreleased glutamate and brief postsynaptic depolarization. This potentiation was N-methyl-d-aspartate receptor (NMDAR)-dependent and was reversed with low-frequency photostimulation in an NMDAR-dependent manner, suggesting that it is mediated by the same mechanism(s) as conventional synaptic long-term potentiation. Potentiation of photolytic responses developed rapidly in a stepwise manner after a brief and variable delay (<60 s) at spines, but could not be induced at extrasynaptic sites on the dendritic shaft. Potentiation was accompanied by a concomitant decrease in postsynaptic, polyamine-dependent paired-pulse facilitation of the photolytic currents, indicating that a change in the subunit composition of the AMPARs underlying the response contributed to the potentiation. These changes are consistent with an increase in the proportion of GluR2-containing AMPARs in the spine head. These results demonstrate that activation of postsynaptic glutamate receptors by glutamate is not only necessary, but sufficient, for the induction of NMDAR-dependent long-term potentiation and reveal additional aspects of its expression.
海马体中，Schaffer侧支-CA1细胞突触兴奋性传递强度的长期增加需要新的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）插入突触，但这一过程的动力学尚未完全明确。利用笼锁谷氨酸的显微光解来激活海马体CA1细胞单个树突棘上的受体，我们发现仅通过一次光释放谷氨酸与短暂的突触后去极化配对，就能使AMPAR介导的电流产生持久增强。这种增强依赖于N-甲基-D-天冬氨酸受体（NMDAR），并能以NMDAR依赖的方式被低频光刺激逆转，这表明它与传统突触长期增强是由相同的机制介导的。光解反应的增强在树突棘短暂且可变的延迟（<60秒）后迅速以逐步方式发展，但在树突干的突触外位点无法诱导。增强伴随着突触后多胺依赖的光解电流配对脉冲易化的同时减少，表明响应所依赖的AMPAR亚基组成的变化促成了增强。这些变化与棘突头部含GluR2的AMPAR比例增加一致。这些结果表明，谷氨酸对突触后谷氨酸受体的激活不仅是诱导NMDAR依赖的长期增强所必需的，而且是充分的，并揭示了其表达的其他方面。
