THE TIMING OF IMPULSE ACTIVITY SHAPES THE PROCESS OF SYNAPTIC COMPETITION AT THE NEUROMUSCULAR JUNCTION
THE TIMING OF IMPULSE ACTIVITY SHAPES THE PROCESS OF SYNAPTIC COMPETITION AT THE NEUROMUSCULAR JUNCTION
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DOI：
10.1016/j.neuroscience.2010.01.055
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发表时间：
2010-05-05
期刊：
影响因子：
3.3
通讯作者：
Busetto, G.
中科院分区：
文献类型：
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作者：
Favero, M.;Buffelli, M.;Busetto, G.
神经肌肉接头的发育表现出深刻的重塑，从以每根肌纤维多个运动神经元输入为特征的不成熟状态转变为成熟的单神经元神经支配。这种惊人的消除过程发生在围产期和成年神经重新支配期间，并且也广泛存在于发育中的中枢神经系统中。各种研究已经表明，冲动活动量对这一过程的加速影响，但也提出了竞争输入中动作电位放电的时间相关性的更微妙的作用。在这里，我们使用神经肌肉接头形成的成年大鼠模型探讨了后者的影响，即运动神经挤压后的神经支配。这与围产期发育具有所有重要特征，尤其是竞争性投入的严格并置。事实上，再生轴突聚集在单个突触后受体簇上，即每根肌纤维的原始终板。在我们之前使用类似范式的实验中，缺少对神经末梢之间竞争的空间方面的关注。我们通过对坐骨神经传导阻滞远端的轴突进行体内电刺激，对竞争终端施加慢性同步放电。对照制剂具有类似的挤压后神经支配，其自然冲动活动不受干扰。我们发现，与对照组相比，实验肌肉表现出较长的多神经元神经支配持续时间，表明赫布机制参与了突触消除过程。我们研究中涉及的另一个方面是成人肌肉再神经支配过程中发生的多神经元神经支配的真实性质，因为它得到共焦显微镜和适当的电生理学测试的支持，这些测试排除了间隙连接对肌纤维的电耦合。 (C) 2010 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
The development of neuromuscular junctions exhibits profound remodeling that brings from an immature state characterized by multiple motoneuronal inputs per muscle fiber, to a mature mononeuronal innervation. This striking elimination process occurs both perinatally and during adult reinnervation, and is also widely present in the developing CNS. The accelerating influence of the amount of impulse activity on this process, has been shown by various studies, but a more subtle role of the time correlation of action potential firing in the competing inputs, has also been suggested. Here we explore the latter influence using a rat adult model of neuromuscular junction formation, that is reinnervation following a motor nerve crush. This shares all important features with perinatal development, especially the strict juxtaposition of the competing inputs. In fact the regenerating axons converge on a single cluster of postsynaptic receptors, that is the original endplate of each muscle fiber. This focus on the spatial aspect of competition between nerve endings was missing in our previous experiments employing a similar paradigm. We impose a chronic synchronous firing to the competing terminals, by in vivo electrical stimulation of their axons distal to a sciatic nerve conduction block. Control preparations, with similar post-crush reinnervation, are left with their natural impulse activity unperturbed. We find that the experimental muscles display a prolonged duration of polyneuronal innervation with respect to controls, indicating that hebbian mechanisms participate in the synapse elimination process. Another aspect dealt with in our study is the genuine nature of the polyneuronal innervation occurring during adult muscle reinnervation, because it is supported by both confocal microscopy and by appropriate electrophysiological tests that exclude electrical coupling of myofibers by gap junctions. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.