Chronic NMDA receptor blockade from birth increases the sprouting capacity of ipsilateral retinocollicular axons without disrupting their early segregation
Chronic NMDA receptor blockade from birth increases the sprouting capacity of ipsilateral retinocollicular axons without disrupting their early segregation
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DOI：
10.1523/jneurosci.21-05-01557.2001
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发表时间：
2001-03-01
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;Constantine-Paton, M
我们研究了NMDAR在大鼠上丘(SSC)视层突触发生过程中结构可塑性的发生和调节中的作用。在这个神经束中，三个投射在发育过程中争夺突触空间。通过荧光标记双眼的投射并用共聚焦显微镜成像，我们可以量化同侧视网膜投射在切除对侧视网膜和/或皮质小脑投射的一部分后的萌发。利用这些技术，我们研究了NMDAR封锁在不同竞争水平下的效果。通过将竞争性拮抗剂2-氨基-5-膦戊酸悬浮在缓释塑料Elvax中，将一片缓释塑料Elvax植入SSC上，从出生后第0天(P0)起长期阻断NMDAR。这种治疗本身并不损害视网膜投射的正常分离。然而，如果同侧投射的萌发始于P6的小的对侧视网膜损伤，这种萌发可以通过从出生起就阻止NMDAR来进一步增加。P10/P11的视网膜损伤也会引起同侧视网膜投射的萌发，但NMDAR阻断剂并不能增加这种后一种损伤所诱导的萌发。然而，当同时消融同侧视皮质时，在NMDAR阻断后，P10/P11损伤显示出更多的萌芽。这些数据表明，阻断P0 NMDAR并不能消除SSC中的突触竞争。相反，早期消除NMDAR功能似乎有助于发芽，而发芽是由其他视觉传入以一种循序渐进的方式进行的。
We have investigated the role of the NMDA glutamate receptor (NMDAR) in the genesis and regulation of structural plasticity during synaptogenesis in the visual layers of the rat superior colliculus (sSC). In this neuropil, three projections compete for synaptic space during development. By fluorescently labeling the projections of both eyes and imaging them with confocal microscopy, we can quantify the sprouting of the ipsilateral retinal projection that follows removal of a portion of the contralateral retinal and/or corticocollicular projection. Using these techniques we have studied the effects of NMDAR blockade under different levels of competition. NMDARs were chronically blocked from birth [postnatal day 0 (P0)] by suspending the competitive antagonist 2-amino-5-phosphonopentanoic acid in the slow release plastic Elvax, a slab of which was implanted over the sSC. Such treatment alone does not impair the normal segregation of the retinal projections. However, if sprouting of the ipsilateral projection is initiated with a small contralateral retinal lesion at P6, this sprouting can be further increased by blocking NMDARs from birth. Sprouting of the ipsilateral retinal projection is also induced by retinal lesions made at P10/P11, but NMDAR blockade does not augment the sprouting induced by this later lesion. However, when combined with simultaneous ablation of the ipsilateral visual cortex, P10/P11 lesions show increased sprouting after NMDAR blockade. These data indicate that P0 NMDAR blockade does not eliminate synaptic competition in the sSC. Instead, early elimination of NMDAR function appears to facilitate sprouting that is gated in a stepwise manner by the other visual afferents.