Dudanova Irina, Tabuchi Katsuhiko, Rohlmann Astrid, Südhof Thomas C, Missler Markus
Department of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.
J Comp Neurol. 2007 May 10;502(2):261-74. doi: 10.1002/cne.21305.
Alpha-neurexins are synaptic cell-surface molecules that are required for Ca(2+)-triggered exocytosis. Mice lacking all three alpha-neurexins show drastically reduced neurotransmitter release at excitatory and inhibitory synapses and die early postnatally. Although previous histological analysis of newborn alpha-neurexin triple mutants revealed only a moderate reduction in the density of type II synapses in the brainstem, cell culture studies proposed that neurexins are prominently involved in synapse formation. To assess the contribution of alpha-neurexins to the formation and structural properties of synapses in vivo, we performed a detailed morphological analysis of the brains from surviving adult double knockout mice lacking two of the three alpha-neurexins. Despite their impaired neurotransmission, we did not observe any gross anatomical defects or changes in the distribution of synaptic proteins in adult mutants. Only mild structural alterations were found: a approximately 20% reduction of neuropil area in many brain regions, resulting predominantly from shortened distal dendritic branches and fewer spines, as demonstrated by Golgi impregnation of pyramidal neurons. Quantitative electron microscopy revealed ultrastructurally normal type I and II terminals and a approximately 30% decrease in the density of type II synapses in the neocortex. To exclude errors in pathfinding, we investigated axonal projections in the olfactory bulb of newborn knockouts and did not observe any changes. Therefore, alpha-neurexins are not essential for the formation of the vast majority of synapses in vivo but rather regulate the function of these synapses.
α-神经连接蛋白是突触细胞表面分子，是Ca(2+)触发的胞吐作用所必需的。缺乏所有三种α-神经连接蛋白的小鼠在兴奋性和抑制性突触处的神经递质释放大幅减少，并在出生后早期死亡。尽管之前对新生α-神经连接蛋白三联突变体的组织学分析仅显示脑干中II型突触密度有适度降低，但细胞培养研究表明神经连接蛋白在突触形成中起重要作用。为了评估α-神经连接蛋白对体内突触形成和结构特性的贡献，我们对存活的成年双敲除小鼠（缺乏三种α-神经连接蛋白中的两种）的大脑进行了详细的形态学分析。尽管它们的神经传递受损，但我们在成年突变体中未观察到任何明显的解剖学缺陷或突触蛋白分布的变化。仅发现了轻微的结构改变：许多脑区的神经毡面积减少了约20%，这主要是由于锥体神经元的高尔基染色显示远端树突分支缩短和棘突减少所致。定量电子显微镜显示I型和II型终末在超微结构上正常，新皮层中II型突触密度降低了约30%。为了排除路径寻找中的错误，我们研究了新生敲除小鼠嗅球中的轴突投射，未观察到任何变化。因此，α-神经连接蛋白对体内绝大多数突触的形成并非必不可少，而是调节这些突触的功能。
