Cell type-specific development of NMDA receptors in the interneurons of rat prefrontal cortex.
Cell type-specific development of NMDA receptors in the interneurons of rat prefrontal cortex.
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DOI：
10.1038/npp.2009.20
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发表时间：
2009-07
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在前额叶皮层，N-甲基-D-天冬氨酸（NMDA）受体不仅对正常的前额叶功能至关重要，而且对精神分裂症的病理过程也至关重要。然而，鲜为人知的是，关于NMDA受体在功能多样的interneurons亚群的发育特性。应用膜片钳技术研究大鼠大脑皮层脑片上前额叶中间神经元NMDA受体的发育变化。我们发现，快速发放（FS）中间神经元的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和NMDA电流的特性与常规发放（RS）和低阈值发放（LTS）中间神经元不同，尤其是在青春期。在幼年动物中，大多数（73%）的FS细胞表现出AMPA和NMDA电流。然而，NMDA电流逐渐变得不可检测的皮质发育过程中，与大多数（74%）的FS细胞表现出没有NMDA电流在成年人。相比之下，RS和LTS中间神经元的AMPA和NMDA电流相对稳定，从青少年到成年没有明显变化。此外，即使在FS细胞与NMDA电流，NMDA/AMPA的比例显着下降，在青少年时期，但返回到青少年的水平，在成年人相比，RS和LTS中间神经元的相对稳定的比例。这些数据表明，FS中间神经元在PFC发生戏剧性的变化，在青春期的多巴胺能受体。这些特性可能使FS细胞对表观遗传刺激特别敏感和脆弱，从而导致许多精神疾病的发作，包括精神分裂症。
In the prefrontal cortex, N-methyl-D-aspartic acid (NMDA) receptors are critical not only for normal prefrontal functions but also for the pathological processes of schizophrenia. Little is known, however, about the developmental properties of NMDA receptors in the functionally diverse subpopulations of interneurons. We investigated the developmental changes of NMDA receptors in rat prefrontal interneurons using patch clamp recording in cortical slices. We found that fast-spiking (FS) interneurons exhibited properties of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA currents distinct from those in regular spiking (RS) and low-threshold spiking (LTS) interneurons, particularly during the adolescent period. In juvenile animals, most (73%) of the FS cells demonstrated both AMPA and NMDA currents. The NMDA currents, however, gradually became undetectable during cortical development, with most (74%) of the FS cells exhibiting no NMDA current in adults. In contrast, AMPA and NMDA currents in RS and LTS interneurons were relatively stable, without significant changes from juveniles to adults. Moreover, even in FS cells with NMDA currents, the NMDA/AMPA ratio dramatically decreased during the adolescent period but returned to juvenile level in adults, compared to the relatively stable ratios in RS and LTS interneurons. These data suggest that FS interneurons in the PFC undergo dramatic changes in glutamatergic receptors during the adolescent period. These properties may make FS cells particularly sensitive and vulnerable to epigenetic stimulation, thus contributing to the onset of many psychiatric disorders, including schizophrenia.
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