Cramer K S, Angelucci A, Hahm J O, Bogdanov M B, Sur M
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Neurosci. 1996 Dec 15;16(24):7995-8004. doi: 10.1523/JNEUROSCI.16-24-07995.1996.
The ferret retinogeniculate projection segregates into eye-specific layers during the first postnatal week and into ON/OFF sublaminae, which receive inputs from either on-center or off-center retinal ganglion cells, during the third and fourth postnatal weeks. The restriction of retinogeniculate axon arbors into eye-specific layers appears to depend on action potential activity () but does not require activation of NMDA receptors (). The formation of ON/OFF sublaminae is also activity-dependent and is disrupted by in vivo blockade of NMDA receptors (). To investigate a possible mechanism whereby blockade of postsynaptic NMDA receptors in the lateral geniculate nucleus (LGN) results in changes in the size and position of presynaptic axon arbors, we tested the role of the diffusible messenger nitric oxide (NO) in the development of the retinogeniculate pathway. We found previously that NO synthase (NOS) is transiently expressed in LGN cells during the refinement of retinogeniculate projections (). In this study, treatment with NG-nitro-L-arginine (L-NoArg), an arginine analog that inhibits NOS, during the third and fourth postnatal weeks resulted in an overall pattern of sublamination that was significantly reduced compared with normal and control animals. Single retinogeniculate axon arbors were located in the middle of eye-specific layers rather than toward the inner or outer half as in normal or control animals. The effect of NOS inhibition was not a consequence of the hypertensive effect of L-NoArg. In contrast to the effect of L-NoArg on the formation of ON/OFF sublaminae, treatment with L-NoArg during the first postnatal week did not disrupt the formation of eye-specific layers. Biochemical assays indicated significant inhibition of NOS during both treatment periods. These data suggest that NO acts together with NMDA receptors in activity-dependent refinement of connections during a specific phase of retinogeniculate development.
雪貂视网膜膝状体投射在出生后的第一周内分离为眼特异性层，并在出生后的第三和第四周内分离为ON/OFF亚层，后者接收来自中心ON或中心OFF视网膜神经节细胞的输入。视网膜膝状体轴突分支在眼特异性层中的限制似乎取决于动作电位活动（），但不需要NMDA受体的激活（）。ON/OFF亚层的形成也依赖于活动，并被体内NMDA受体的阻断所破坏（）。为了研究外侧膝状体核（LGN）中突触后NMDA受体的阻断导致突触前轴突分支大小和位置变化的可能机制，我们测试了可扩散信使一氧化氮（NO）在视网膜膝状体通路发育中的作用。我们之前发现，在视网膜膝状体投射细化过程中，NO合酶（NOS）在LGN细胞中短暂表达（）。在这项研究中，在出生后的第三和第四周用NG-硝基-L-精氨酸（L-NoArg）（一种抑制NOS的精氨酸类似物）进行处理，导致与正常和对照动物相比，亚层化的总体模式显著减少。单个视网膜膝状体轴突分支位于眼特异性层的中间，而不是像正常或对照动物那样朝向内侧或外侧一半。NOS抑制的作用不是L-NoArg的高血压作用的结果。与L-NoArg对ON/OFF亚层形成的影响相反，在出生后的第一周用L-NoArg进行处理并没有破坏眼特异性层的形成。生化分析表明，在两个处理期内NOS均受到显著抑制。这些数据表明，在视网膜膝状体发育的特定阶段，NO与NMDA受体一起在活动依赖性连接细化中发挥作用。
