PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex
PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex
复制标题
DOI：
10.1113/jphysiol.2002.031369
复制
发表时间：
2003-02-01
影响因子：
5.5
通讯作者：
Andrade, R
中科院分区：
文献类型：
--
作者：
Béïque, JC;Andrade, R
PSD-95是在兴奋性突触的突触后密度中发现的最丰富的蛋白质之一。然而，PSD-95在调节突触传递和可塑性中所起的确切功能作用仍不清楚。为了解决这个问题，我们已经过表达PSD-95在皮质锥体神经元的器官型脑切片使用粒子介导的基因转移和评估的后果突触传递和可塑性。在+40 mV记录的诱发EPSC的AMPA受体/NMDA受体（AMPAR/NMDAR）的比率在PSD-95转染的锥体神经元中大于对照。这种差异不能解释为AMPAR介导的突触电流整流的变化，因为在对照组和PSD-95转染的神经元中获得的电流-电压曲线是不可区分的。然而，AMPAR介导的诱发EPSC的振幅在PSD-95转染的神经元中比匹配的对照组更大。配对脉冲比分析表明，PSD-95的过表达并不改变突触前释放概率。PSD-95的转染进一步伴随着AMPAR介导的mEPSC的频率而不是幅度的增加。总之，这些结果表明PSD-95的转染增加了AMPAR介导的突触传递。此外，他们认为这种现象反映了表达AMPAR的突触数量的增加，而不是这些受体在单个突触上的数量或功能的增加。我们测试了这些变化对突触可塑性的影响，发现PSD-95转染大大提高了观察长期抑郁的可能性。因此，这些结果确定了PSD-95的生理作用，并证明这种蛋白质可以在控制突触强度和活性依赖性突触可塑性中发挥决定性作用。
PSD-95 is one of the most abundant proteins found in the postsynaptic density of excitatory synapses. However, the precise functional role played by PSD-95 in regulating synaptic transmission and plasticity remains undefined. To address this issue, we have overexpressed PSD-95 in cortical pyramidal neurons in organotypic brain slices using particle-mediated gene transfer and assessed the consequences on synaptic transmission and plasticity. The AMPA receptor/NMDA receptor (AMPAR/NMDAR) ratio of evoked EPSCs recorded at +40 mV was greater in PSD-95-transfected pyramidal neurons than in controls. This difference could not be accounted for by a change in rectification of AMPAR-mediated synaptic currents since the current-voltage curves obtained in controls and in PSD-95-transfected neurons were indistinguishable. However, the amplitude of AMPAR-mediated evoked EPSCs was larger in PSD-95-transfected neurons compared to matched controls. Paired-pulse ratio analysis suggested that overexpression of PSD-95 did not alter presynaptic release probability. Transfection of PSD-95 was further accompanied by an increase in the frequency, but not amplitude, of AMPAR-mediated mEPSCs. Together, these results indicate that transfection of PSD-95 increased AMPAR-mediated synaptic transmission. Furthermore, they suggest that this phenomenon reflects an increased number of synapses expressing AMPARs rather than an increased number or function of these receptors at individual synapses. We tested the consequences of these changes on synaptic plasticity and found that PSD-95 transfection greatly enhanced the probability of observing long-term depression. These results thus identify a physiological role for PSD-95 and demonstrate that this protein can play a decisive role in controlling synaptic strength and activity-dependent synaptic plasticity.