The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release
The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release
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DOI：
10.1073/pnas.0630290100
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发表时间：
2003-04-15
影响因子：
11.1
通讯作者：
Lisman, J
中科院分区：
文献类型：
--
作者：
Conti, R;Lisman, J
我们对中枢突触传递的大部分认识都是通过研究突触群体获得的，但突触的一些重要性质只能通过单独研究来确定。一个重要的问题是，突触前动作电位是否最多导致单个囊泡释放，或者多量子传输是否可能。先前在CA 1区的研究表明，对单个轴突刺激的反应可能是高度可变的，显然是因为它由可变数量的量子元素组成（振幅约为5 pA）。这些量子事件具有低变异系数（CV）。由于涉及的突触接触的数量是未知的，这种反应可能是由于在不同数量的突触上的单量子传输，或者是由于在单个突触上的多量子传输。前者预测，在个别突触的CV应该是小的。我们已经使用光学方法来测量N-甲基-D-天冬氨酸受体介导的Ca 2+升高在单个活动突触。我们的主要发现是，非故障响应的幅度可能是高度可变的，具有高达0.63的CV。在一个偶然的实验中，光学研究的突触是唯一活跃的突触，因此我们可以测量其N-甲基-D-天冬氨酸（NMDA）受体和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体介导的信号。在这个突触上，两种信号的变化范围超过10倍，并且高度相关。这些结果有力地表明，在单个CA 1突触的传输可以是多量子的。此外，单个量子响应距离饱和非常远，允许许多量子的有效总和。多量子释放的存在对于定义突触强度和理解突触可塑性机制具有重要意义。
Most of our knowledge about transmission at central synapses has been obtained by studying populations of synapses, but some important properties of synapses can be determined only by studying them individually. An important issue is whether a presynaptic action potential causes, at most, a single vesicle to be released, or whether multiquantal transmission is possible. Previous work in the CA1 region has shown that the response to stimulation of a single axon can be highly variable, apparently because it is composed of a variable number of quantal elements (approximate to 5 pA in amplitude). These quantal events have a low coefficient of variation (CV). Because the number of synaptic contacts involved is not known, the response could be because of uniquantal transmission at a varying number of synapses, or to multliquantal transmission at a single synapse. The former predicts that the CV at individual synapses should be small. We have used optical methods to measure the N-methyl-D-aspartate receptor-mediated Ca2+ elevation at single active synapses. Our main finding is that the amplitude of nonfailure responses could be highly variable, having a CV as large as 0.63. In one fortuitous experiment, the optically studied synapse was the only active synapse, and we could therefore measure both its N-methyl-D-aspartate (NMDA) receptor and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated signals. At this synapse, both signals varied over a 10-fold range and were highly correlated. These results strongly suggest that transmission at single CA1 synapses can be multiquantal. Furthermore, the individual quantal response is very far from saturation, allowing the effective summation of many quanta. The existence of multiquantal release has important implications for defining synaptic strength and understanding the mechanisms of synaptic plasticity.