Nusser Z, Hájos N, Somogyi P, Mody I
Medical Research Council, Department of Pharmacology, University of Oxford, UK.
Nature. 1998 Sep 10;395(6698):172-7. doi: 10.1038/25999.
Changes in synaptic efficacy are essential for neuronal development, learning and memory formation and for pathological states of neuronal excitability, including temporal-lobe epilepsy. At synapses, where there is a high probability of opening of postsynaptic receptors, all of which are occupied by the released transmitter, the most effective means of augmenting postsynaptic responses is to increase the number of receptors. Here we combine quantal analysis of evoked inhibitory postsynaptic currents with quantitative immunogold localization of synaptic GABA(A) receptors in hippocampal granule cells in order to clarify the basis of inhibitory synaptic plasticity induced by an experimental model of temporal-lobe epilepsy (a process known as kindling). We find that the larger amplitude (66% increase) of elementary synaptic currents (quantal size) after kindling results directly from a 75% increase in the number of GABA(A) receptors at inhibitory synapses on somata and axon initial segments. Receptor density was up by 34-40% and the synaptic junctional area was expanded by 31%. Presynaptic boutons were enlarged, which may account for the 39% decrease in the average number of released transmitter packets (quantal content). Our findings establish the postsynaptic insertion of new GABA(A) receptors and the corresponding increase in postsynaptic responses augmenting the efficacy of mammalian inhibitory synapses.
突触效能的变化对于神经元发育、学习和记忆形成以及包括颞叶癫痫在内的神经元兴奋性病理状态至关重要。在突触处，突触后受体开放的概率很高，且所有受体均被释放的递质占据，增强突触后反应最有效的方法是增加受体数量。在此，我们将诱发抑制性突触后电流的量子分析与海马颗粒细胞中突触GABA(A)受体的定量免疫金定位相结合，以阐明颞叶癫痫实验模型（一种称为点燃的过程）诱导的抑制性突触可塑性的基础。我们发现，点燃后初级突触电流（量子大小）幅度增大（增加66%）直接源于胞体和轴突起始段抑制性突触处GABA(A)受体数量增加75%。受体密度提高了34 - 40%，突触连接面积扩大了31%。突触前终扣增大，这可能是释放的递质小包平均数量（量子含量）减少39%的原因。我们的研究结果证实了新的GABA(A)受体在突触后插入以及相应的突触后反应增加，增强了哺乳动物抑制性突触的效能。
