From plaque to pretzel: Fold formation and acetylcholine receptor loss at the developing neuromuscular junction
From plaque to pretzel: Fold formation and acetylcholine receptor loss at the developing neuromuscular junction
复制标题
DOI：
10.1523/jneurosci.20-10-03663.2000
复制
发表时间：
2000-05-15
影响因子：
5.3
通讯作者：
Lichtman, JW
中科院分区：
文献类型：
--
作者：
Marques, MJ;Conchello, JA;Lichtman, JW
虽然在理解突触形成的最初步骤方面取得了进展，但对其随后的成熟知之甚少（Sanes和Lichtman，1999）。哺乳动物神经肌肉接头的突触后侧的两个改变发生在出生后的早期：乙酰胆碱受体（AChRs）从发育中的接头的部分消失，因为除了一个轴突输入被删除，和突触后膜的地形变得更加复杂的沟槽和褶皱的建立。我们通过使用反射光共聚焦显微镜以一种新的方式对小鼠神经肌肉接头处标记的AChR进行成像，同时研究了AChR分布和突触后地形图的成熟。在出生时，突触后受体定位在匙形斑块内的不规则斑块中。几天后开始，受体区域内的一个单一的终板分为分化和组织较少的车厢。在发育中的沟槽中可以看到通常与肌纤维长轴正交的褶皱，尽管沟槽的方向似乎是由神经的分支模式强加的。最终，缺乏AChR标记的浅表区域在所有连接处都很明显。在路口失神经支配的新生儿期沟的形成和表面受体区域的消失被阻止。我们认为，生长中的肌纤维和粘附在其上的相对无弹性的突触末梢之间的张力导致了突触后膜的地形特征。这个观点为神经递质释放部位的沟、褶皱和褶皱的位置提供了一个力学解释。
Although there has been progress in understanding the initial steps in the formation of synapses, less is known about their subsequent maturation (Sanes and Lichtman, 1999). Two alterations on the postsynaptic side of the mammalian neuromuscular junction occur during early postnatal life: acetylcholine receptors (AChRs) disappear from parts of the developing junction as all but one axonal inputs are removed, and the topography of the postsynaptic membrane becomes more complicated as gutters and folds are established. We have studied the maturation of the AChR distribution and postsynaptic topography simultaneously by imaging labeled AChRs at the mouse neuromuscular junction in a new way, using reflected light confocal microscopy. At birth postsynaptic receptors were localized in irregular patches within a spoon-shaped plaque. Beginning several days later, receptor regions within a single endplate were divided into differentiated and less organized compartments. Folds generally oriented orthogonal to the long axis of the muscle fiber were seen in developing gutters, although the orientation of the gutters seemed to be imposed by the branching pattern of the nerve. Eventually, superficial regions lacking AChR labeling were apparent in all junctions. In junctions denervated in the neonatal period both gutter formation and the disappearance of superficial receptors regions were prevented. We suggest that tension between growing muscle fibers and the relatively inelastic synaptic terminals that adhere to them causes the topographic features of the postsynaptic membrane. This view provides a mechanical explanation for gutters, folds, and the location of folds at sites of neurotransmitter release.