Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse
Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse
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DOI：
10.1523/jneurosci.20-12-04423.2000
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发表时间：
2000-06-15
影响因子：
5.3
通讯作者：
Regehr, WG
中科院分区：
文献类型：
--
作者：
Carter, AG;Regehr, WG
尽管神经元经常突然放电，但大多数关于谷氨酸信号和突触后受体激活的已知信息都是基于使用单一刺激的实验。在这里，我们研究了在平行纤维到星状细胞突触的爆发处对离子型谷氨酸受体的激活。我们发现，短暂的刺激序列产生了AMPA受体(AMPAR)和NMDA受体(NMDAR)介导的延长的EPSCs，记录在全细胞电压钳上。这些EPSC与AMPAR介导的由单一刺激引起的快速EPSC形成对比。延长的AMPAR介导的EPSC由高频和高强度的列车促进，并可以持续数百毫秒。谷氨酸转运体的抑制剂L-反式-2，4-磷酸脱氢酶也增加了这种EPSC，这表明这些转运体通常限制了对火车的突触反应。这些延长的EPSCs既反映了受体的特性，也反映了持久的谷氨酸信号。此外，一些实验表明，谷氨酸溢出可以促进受体激活。首先，成像刺激诱发的突触前钙变化建立了明显的平行纤维带可以被激活。其次，激活不直接与给定星状细胞突触的平行纤维可以在该细胞中激发间接的AMPAR和NMDAR介导的EPSCs。第三，使用依赖使用的NMDAR阻滞剂MK-801的实验表明，这些间接的EPSCs反映了谷氨酸溢出对火车的反应。综上所述，这些发现表明，刺激序列可以产生持续和广泛的谷氨酸信号，进而可以激发由离子型谷氨酸受体介导的大而长的EPSCs。这些突触特性可能对星状细胞的放电有重要的功能影响。
Although neurons often fire in bursts, most of what is known about glutamate signaling and postsynaptic receptor activation is based on experiments using single stimuli. Here we examine the activation of ionotropic glutamate receptors by bursts at the parallel fiber to stellate cell synapse. We show that brief stimulus trains generate prolonged AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated EPSCs recorded in whole-cell voltage clamp. These EPSCs contrast with the rapid AMPAR-mediated EPSC evoked by a single stimulus. The prolonged AMPAR-mediated EPSC is promoted by high-frequency and high-intensity trains and can persist for hundreds of milliseconds. This EPSC is also increased by L-trans-2,4-PDC, an inhibitor of glutamate transporters, suggesting that these transporters usually limit the synaptic response to trains. These prolonged EPSCs reflect both receptor properties and a longlasting glutamate signal. In addition, several experiments demonstrate that glutamate spillover can contribute to receptor activation. First, imaging stimulus-evoked changes in presynaptic calcium establishes that distinct parallel fiber bands can be activated. Second, activation of parallel fibers that do not directly synapse onto a given stellate cell can evoke indirect AMPAR- and NMDAR-mediated EPSCs in that cell. Third, experiments using the use-dependent NMDAR blocker MK-801 show that these indirect EPSCs reflect glutamate spillover in response to trains. Together, these findings indicate that stimulus trains can generate a sustained and widespread glutamate signal that can in turn evoke large and prolonged EPSCs mediated by ionotropic glutamate receptors. These synaptic properties may have important functional consequences for stellate cell firing.