NMDA receptor currents suppress synapse formation on sprouting axons in vivo
NMDA receptor currents suppress synapse formation on sprouting axons in vivo
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DOI：
10.1523/jneurosci.4063-04.2005
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发表时间：
2005-02-02
影响因子：
5.3
通讯作者：
Constantine-Paton, M
中科院分区：
文献类型：
--
作者：
Colonnese, MT;Zhao, JP;Constantine-Paton, M
NMDA 受体（NMDAR）在突触的结构维持和功能强度中发挥着重要作用。这些解剖学和功能作用之间的因果关系尚不清楚。使用定量共聚焦显微镜、突触小泡免疫反应性和视网膜投影的差异标记，我们测量了8天前沿同侧视网膜轴突（ipsi轴突）萌芽到上丘（sSC）浅表视觉层的轴突体积和突触密度，该上丘（sSC）被对侧视网膜病变（暗点）阻滞。当出生后第 6 天 (P6) 发生视网膜损伤时，暗点内神经元上的谷氨酸突触电流显着减少。 NMDAR 的长期 D-AP-5 拮抗作用增加了 ipsi 轴突萌芽和突触密度。相反，长期暴露于激动剂 NMDA 会降低 ipsi 轴突萌芽和突触密度，已知 NMDA 可以在功能上抑制该系统中的谷氨酸传输。然而，在 P11 损伤后，NMDAR 阻断对萌芽或突触密度没有影响。 NMDAR 当前动力学的发育变化无法解释 NMDAR 功能结构效应的这种差异。此外，P11 损伤后暗点内的突触电流频率没有受到影响。皮质小球投射在 P11 生存间隔期间成熟，并且如之前的工作所示，它是突触空间竞争的来源，并且可能是较老的 sSC 中维持活动的来源。因此，我们的结果表明，在早期发育过程中，NMDAR 电流主要破坏新生突触的稳定性。然而，随着神经纤维的成熟，无论 NMDAR 功能如何，对突触空间的竞争都会抑制轴突萌芽和突触形成。
NMDA receptors (NMDARs) play an important role in the structural maintenance and functional strength of synapses. The causal relationship between these anatomical and functional roles is poorly defined. Using quantitative confocal microscopy, synaptic vesicle immunoreactivity, and differential label of retinal projections, we measured axon volume and synapse density along ipsilateral retinal axons (ipsi axons) sprouting into the superficial visual layers of the superior colliculus (sSC) deafferented by a contralateral retinal lesion ( a scotoma) 8 d earlier. When retinal lesions were made at postnatal day 6 (P6), glutamatergic synaptic currents on neurons within the scotoma were significantly reduced. Both ipsi axon sprouting and synapse density were increased by chronic D-AP-5 antagonism of NMDARs. Conversely, ipsi axon sprouting and synapse density were reduced by chronic exposure to the agonist, NMDA, known to functionally depress glutamate transmission in this system. After P11 lesions, however, NMDAR blockade had no effect on sprouting or synapse density. Developmental changes in NMDAR current kinetics could not account for this difference in the structural effects of NMDAR function. Also, synaptic current frequencies within the scotoma were not affected after the P11 lesions. The corticocollicular projection matures during the P11 survival interval and, as indicated by previous work, it is a source of competition for synaptic space and probably of maintained activity in the older sSC. Thus, our results suggest that during early development, NMDAR currents predominantly destabilize nascent synapses. As the neuropil matures, however, competition for synaptic space suppresses axon sprouting and synapse formation regardless of NMDAR function.