NMDA receptor-mediated refinement of a transient retinotectal projection during development requires nitric oxide
NMDA receptor-mediated refinement of a transient retinotectal projection during development requires nitric oxide
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DOI：
10.1523/jneurosci.19-01-00229.1999
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发表时间：
1999-01-01
影响因子：
5.3
通讯作者：
McLoon, SC
中科院分区：
文献类型：
--
作者：
Ernst, AF;Wu, HH;McLoon, SC
短暂的同侧视网膜顶盖投射通常在雏鸡视觉系统的胚胎发育过程中被消除。在该投射通常消失的发育期施用 NMDA 受体拮抗剂 5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺 (MK-801) 可阻止其完全消除。先前的研究表明，顶盖细胞在发育过程中表达一氧化氮合酶，阻断一氧化氮的合成也会阻止同侧视网膜顶盖投射的消除。在鸡胚中通过生化方法评估了 NMDA 受体阻断对顶盖细胞中一氧化氮合酶活性的影响。 MK-801 浓度的增加导致一氧化氮合酶活性呈剂量依赖性下降。这一结果表明 NMDA 受体激活可以调节顶盖中一氧化氮合酶的活性。在用 MK-801 或一氧化氮合成抑制剂 N omega-硝基-L-精氨酸 (L-NoArg) 处理的胚胎中比较同侧视网膜顶盖投射的挽救程度。在一氧化氮合成抑制水平相当的情况下，NMDA 受体阻断或一氧化氮合成阻断介导的救援程度没有观察到显着差异。这些结果表明，NMDA 受体介导的同侧视网膜顶盖投射消除完全是通过一氧化氮介导的。
A transient ipsilateral retinotectal projection is normally eliminated during embryonic development of the chick visual system. Administration of the NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) during the developmental period in which this projection normally disappears prevented its complete elimination. Previous studies showed that tectal cells express nitric oxide synthase during development, and blocking synthesis of nitric oxide also prevented elimination of the ipsilateral retinotectal projection. The effect of NMDA receptor blockade on nitric oxide synthase activity in tectal cells was assessed biochemically in chick embryos. Increasing concentrations of MK-801 resulted in a dose-dependent decrease in nitric oxide synthase activity. This result suggests that NMDA receptor activation can regulate nitric oxide synthase activity in the tectum. The degree of rescue of the ipsilateral retinotectal projection was compared in embryos treated either with MK-801 or with an inhibitor of nitric oxide synthesis, N omega-nitro-L-arginine (L-NoArg). At comparable levels of inhibition of nitric oxide synthesis, no significant difference was observed in the degree of rescue mediated by NMDA receptor blockade or nitric oxide synthesis blockade. These results suggest that NMDA receptor-mediated elimination of the ipsilateral retinotectal projection is completely mediated via nitric oxide.