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d-Serine differently modulates NMDA receptor function in rat CA1 hippocampal pyramidal cells and interneurons

机译:d-丝氨酸在大鼠CA1海马锥体细胞和中间神经元中调节NMDA受体功能

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摘要

The organization of the neuronal hippocampal network depends on the tightly regulated interaction between pyramidal cells (PCs) and interneurons (Ints). NMDA receptor (NMDAR) activation requires the binding of glutamate and co-activation of the ‘glycine site’. It has been reported that d-serine is a more potent endogenous agonist than glycine for that site. While many studies have focused on NMDAR function in PCs, little is known regarding the modulation of NMDARs in Ints. We studied the modulatory effect of d-serine on NMDAR EPSCs in PCs and in stratum radiatum Ints using whole-cell patch-clamp recording in rat acute hippocampal slices. We found that d-serine enhances NMDAR function and differently modulates NMDAR currents in both cell types. The augmentation of NMDAR currents by d-serine was significantly larger in PCs compared with Ints. Moreover, we found differences in the kinetics of NMDAR currents in PCs and Ints. Our findings indicate that regulation of NMDAR through the ‘glycine site’ depends on the cell types. We speculate that the observed differences arise from assemblies of diverse NMDAR subunits. Overall, our data suggest that d-serine may be involved in regulation of the excitation-inhibition balance in the CA1 hippocampal region.
机译:神经元海马网络的组织取决于锥体细胞(PC)和神经元(Ints)之间紧密调节的相互作用。 NMDA受体(NMDAR)的激活需要结合谷氨酸并共同激活“甘氨酸位点”。据报道,对于该位点,d-丝氨酸比甘氨酸是更有效的内源性激动剂。尽管许多研究集中在PC上的NMDAR功能,但对于Ints中NMDAR的调制知之甚少。我们使用全细胞膜片钳记录在大鼠急性海马切片中研究了d-丝氨酸对PCs和放射状层中NMDAR EPSC的调节作用。我们发现,在两种细胞类型中,d-丝氨酸都增强了NMDAR功能,并不同地调节NMDAR电流。与Ints相比,在PC中,d-丝氨酸对NMDAR电流的增加明显更大。此外,我们发现PC和Ints中NMDAR电流的动力学差异。我们的发现表明,通过“甘氨酸位点”调节NMDAR取决于细胞类型。我们推测观察到的差异是由各种NMDAR亚基的组装引起的。总体而言,我们的数据表明,d-丝氨酸可能参与了CA1海马区的兴奋抑制平衡调节。

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