Andrásfalvy Bertalan K, Magee Jeffrey C
Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
J Physiol. 2004 Sep 1;559(Pt 2):543-54. doi: 10.1113/jphysiol.2004.065219. Epub 2004 Jul 2.
In the CA1 region of the hippocampus, LTP is thought to be initiated by a transient activation of NMDA receptors and is expressed as a persistent increase in synaptic transmission through AMPA receptors. To investigate the postsynaptic modifications of AMPA receptors involved in this enhanced synaptic transmission, the channel density and single-channel properties of extrasynaptic AMPA receptors located in synaptically active dendritic regions were examined following the induction of LTP. Following tetanic stimulation an outside-out patch was excised from the apical dendrite near the point of stimulation and saturating concentrations of glutamate were rapidly applied to the patch. AMPA current amplitude and duration were increased significantly in patches pulled from dendrites that expressed LTP. Non-stationary fluctuation analysis of AMPA currents indicated that AMPA channel number was nearly twofold larger than in controls, while single channel conductance and maximum open-probability were unchanged. Furthermore, while subtle changes in AMPA channel kinetics could also be observed, we did not find any evidence that receptor affinity or rectification properties were altered by LTP induction. Very similar results were found when CaMK-II activity was increased through the intracellular application of Ca/CaM. Together, we interpret our data to indicate that the stimuli used here produce an increased delivery of AMPA receptors to synaptically active regions of the apical dendrite without inducing any significant changes in their basic biophysical properties and that such delivery is a key element in this form of synaptic plasticity.
在海马体的CA1区域,长时程增强(LTP)被认为是由NMDA受体的短暂激活引发的,并表现为通过AMPA受体的突触传递持续增加。为了研究参与这种增强的突触传递的AMPA受体的突触后修饰,在诱导LTP后,检测了位于突触活跃树突区域的突触外AMPA受体的通道密度和单通道特性。强直刺激后,从刺激点附近的顶端树突切除一个outside-out膜片,并将饱和浓度的谷氨酸迅速施加到该膜片上。从表达LTP的树突中获取的膜片中,AMPA电流幅度和持续时间显著增加。对AMPA电流的非平稳波动分析表明,AMPA通道数量比对照组几乎大两倍,而单通道电导和最大开放概率没有变化。此外,虽然也能观察到AMPA通道动力学的细微变化,但我们没有发现任何证据表明LTP诱导会改变受体亲和力或整流特性。当通过细胞内应用Ca/CaM增加CaMK-II活性时,也发现了非常相似的结果。总之,我们对数据的解释表明,这里使用的刺激使AMPA受体向顶端树突的突触活跃区域的递送增加,而不会在其基本生物物理特性上诱导任何显著变化,并且这种递送是这种形式的突触可塑性的关键因素。