Synaptically released glutamate activates extrasynaptic NMDA receptors on cells in the ganglion cell layer of rat retina
Synaptically released glutamate activates extrasynaptic NMDA receptors on cells in the ganglion cell layer of rat retina
复制标题
DOI：
10.1523/jneurosci.22-06-02165.2002
复制
发表时间：
2002-03-15
影响因子：
5.3
通讯作者：
Diamond, JS
中科院分区：
文献类型：
--
作者：
Chen, S;Diamond, JS
NMDA和AMPA受体（NMDARs和AMPARs）共定位于中枢神经系统的大多数兴奋性突触。因此，这两种受体类型都被单一量子的递质激活，并有助于微型和诱发epsc。然而，在两栖动物视网膜中，神经节细胞层神经元中的微型EPSCs仅由AMPARs介导，尽管NMDARs和AMPARs在诱发EPSCs时都被激活。对这种差异的一种解释是，NMDARs位于突触间隙之外，只有当突触外谷氨酸水平在多个突触同时释放时增加时才被激活。另外，NMDARs可能在突触中分离，这些突触要么不是自发活动的，要么产生微小的EPSCs，这些EPSCs太小而无法检测到。在本研究中，我们检测了大鼠视网膜急性切片神经节细胞层神经元的兴奋性、谷氨酸能突触输入。通过电刺激突触前双极细胞诱导的EPSCs表现出NMDAR和ampar介导的成分。然而，自发EPSCs仅表现出ampar介导的成分。低亲和力、竞争性受体拮抗剂的作用表明，在诱发的突触反应中，NMDARs遇到的谷氨酸比ampar少。减少谷氨酸摄取或改变释放概率优先影响诱发EPSCs的NMDAR成分；减少摄取表明自发性EPSCs中存在NMDAR成分。这些结果表明NMDAR位于突触外，谷氨酸转运体阻止NMDAR被单个囊泡释放的递质激活，并限制其在诱发反应中的激活。
NMDA and AMPA receptors (NMDARs and AMPARs) are colocalized at most excitatory synapses in the CNS. Consequently, both receptor types are activated by a single quantum of transmitter and contribute to miniature and evoked EPSCs. However, in amphibian retina, miniature EPSCs in ganglion cell layer neurons are mediated solely by AMPARs, although both NMDARs and AMPARs are activated during evoked EPSCs. One explanation for this discrepancy is that NMDARs are located outside of the synaptic cleft and are activated only when extrasynaptic glutamate levels increase during coincident release from multiple synapses. Alternatively, NMDARs may be segregated at synapses that either are not spontaneously active or yield miniature EPSCs that are too small to detect. In this study, we examined excitatory, glutamatergic synaptic inputs to neurons in the ganglion cell layer of acute slices of rat retina. EPSCs, elicited by electrically stimulating presynaptic bipolar cells, exhibited both NMDAR- and AMPAR-mediated components. However, spontaneous EPSCs exhibited only an AMPAR-mediated component. The effects of low-affinity, competitive receptor antagonists indicated that NMDARs encounter less glutamate than AMPARs during an evoked synaptic response. Reducing glutamate uptake or changing the probability of release preferentially affected the NMDAR component in evoked EPSCs; reducing uptake revealed an NMDAR component in spontaneous EPSCs. These results indicate that NMDARs are located extrasynaptically and that glutamate transporters prevent NMDAR activation by a transmitter released from a single vesicle and limit their activation during evoked responses.