Synapse-specific expression of functional presynaptic NMDA receptors in rat somatosensory cortex
Synapse-specific expression of functional presynaptic NMDA receptors in rat somatosensory cortex
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DOI：
10.1523/jneurosci.3915-07.2008
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发表时间：
2008-02-27
影响因子：
5.3
通讯作者：
Feldman, Daniel E.
中科院分区：
文献类型：
--
作者：
Brasier, Daniel J.;Feldman, Daniel E.
突触前NMDA受体（NMDAR）调节了许多谷氨酸能突触的释放和可塑性，但是尚未检查其在突触类别中表达的特异性。我们发现，非poStsynaptic，可能含有突触的NR2B前NMDARS增强了AMPA受体介导的突触传播，在少年大鼠桶皮层中4（L4）至L2/3（L4）至L2/3（L4-L2/3）突触。当通过细胞外谷氨酸或外源性NMDAR激动剂的应用激活突触前NMDAR时，这种调节在室温下显而易见。在接近生理温度下，自然发生了突触前NMDAR的传播，而无需外部激活。在L4 -L2/3突触下，突触前NMDARS抑制单一和细胞外EPSC的阻塞，并伴随着成对的脉冲比和变异系数的增加，表明突触前释放概率的降低。 NMDAR激动剂增加了L2/3神经元中微型EPSC的频率，而不会改变其振幅或动力学。 NMDAR拮抗剂的焦点应用显示，调节L4-L2/3传输的NMDAR位于L2/3而不是L4中，与L4-L2/3突触的终端或轴突的定位一致，而不是在Somato Dendritic隔间上突触前的L4神经元。相比之下，突触前NMDAR不调节L4 -L4突触，该突触来自与L4-L2/3突触的同一突触前神经元，或横柱l2/3-L2/3水平投影，它们突触到同一突触后神经元突触。因此，相对于由同一神经元制成的其他突触，突触前NMDAR选择性调节L4-L2/3突触。这些受体的存在可能支持L4-L2/3突触的专业加工或可塑性。
Presynaptic NMDA receptors ( NMDARs) modulate release and plasticity at many glutamatergic synapses, but the specificity of their expression across synapse classes has not been examined. We found that non-postsynaptic, likely presynaptic NR2B-containing NMDARs enhanced AMPA receptor-mediated synaptic transmission at layer 4 ( L4) to L2/3 ( L4-L2/3) synapses in juvenile rat barrel cortex. This modulation was apparent at room temperature when presynaptic NMDARs were activated by elevation of extracellular glutamate or application of exogenous NMDAR agonists. At near physiological temperatures, modulation of transmission by presynaptic NMDARs occurred naturally, without the need for external activation. Blockade of presynaptic NMDARs depressed unitary and extracellularly evoked EPSCs at L4 -L2/3 synapses, accompanied by increases in paired-pulse ratio and coefficient of variation, indicative of a decrease in presynaptic release probability. NMDAR agonists increased the frequency of miniature EPSCs in L2/3 neurons, without altering their amplitude or kinetics. Focal application of NMDAR antagonist revealed that the NMDARs that modulate L4-L2/3 transmission are located in L2/3, not L4, consistent with localization on terminals or axons of L4-L2/3 synapses, rather than on the somato-dendritic compartment of presynaptic L4 neurons. In contrast, presynaptic NMDARs did not modulate L4 -L4 synapses, which originate from the same presynaptic neurons as L4-L2/3 synapses, or cross-columnar L2/3-L2/3 horizontal projections, which synapse onto the same postsynaptic target neurons. Thus, presynaptic NMDARs selectively modulate L4-L2/3 synapses, relative to other synapses made by the same neurons. Existence of these receptors may support specialized processing or plasticity by L4-L2/3 synapses.