English A W, Schwartz G
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Dev Biol. 1995 May;169(1):57-64. doi: 10.1006/dbio.1995.1126.
At birth, nearly all rat muscle fibers receive synaptic inputs from more than one motoneuron at a single end-plate site. By the end of the third postnatal week all but one of these inputs has been eliminated. During this loss of polyneuronal innervation, developing neuromuscular synapses compete with one another. Although the nature of this competition is not known, it is commonly assumed that it is mediated through differential activity of the competing inputs. One means by which such differential activity might be translated into a biological signal would be if the synapses compete in an activity-dependent manner for a scarce supply of neurotrophic molecules. A prediction of this hypothesis is that excess quantities of such trophic molecules will reduce competition and thereby slow down or abolish the normal loss of polyneuronal innervation. In newborn rats, the effects of injection of either basic fibroblast growth factor (bFGF) or ciliary neurotrophic factor (CNTF) on the outcome of neuromuscular synapse elimination were investigated. Daily injections of either bFGF or CNTF were made for 1 week into the lateral gastrocnemius muscle beginning at the postnatal age of 2 days. The amount of polyneuronal innervation of fibers in trophic molecule-injected muscles and saline-injected contralateral muscles was assayed using intracellular recording methods. For both bFGF- and CNTF-injected muscles, an increase in the percentage of polyneuronally innervated fibers relative to saline-injected muscles was noted. For bFGF-injected muscles, the amount of polyneuronal innervation remained at nearly 60% as late as the postnatal age of 14 days (P14). This is the amount of polyneuronal innervation found at age 6 days in normal animals. Nearly 40% of the fibers of CNTF-injected muscles remained polyneuronally innervated at age P14, the amount expected at age 9 days. These results indicate that both bFGF and CNTF exert powerful and long-lasting effects on developing neuromuscular synapses.
出生时，几乎所有大鼠肌肉纤维在单个终板部位接受来自多个运动神经元的突触输入。到出生后第三周结束时，除了其中一个输入外，其他所有输入都已被消除。在多神经元支配丧失的过程中，发育中的神经肌肉突触相互竞争。尽管这种竞争的本质尚不清楚，但通常认为它是通过竞争输入的差异活动介导的。这种差异活动可能转化为生物信号的一种方式是，如果突触以活动依赖的方式竞争稀缺的神经营养分子供应。该假设的一个预测是，过量的此类营养分子将减少竞争，从而减缓或消除多神经元支配的正常丧失。在新生大鼠中，研究了注射碱性成纤维细胞生长因子（bFGF）或睫状神经营养因子（CNTF）对神经肌肉突触消除结果的影响。从出生后2天开始，每天向外侧腓肠肌注射bFGF或CNTF，持续1周。使用细胞内记录方法测定注射营养分子的肌肉和注射生理盐水的对侧肌肉中纤维的多神经元支配量。对于注射bFGF和CNTF的肌肉，相对于注射生理盐水的肌肉，多神经元支配纤维的百分比均有所增加。对于注射bFGF的肌肉，直到出生后14天（P14），多神经元支配量仍接近60%。这是正常动物6天时的多神经元支配量。在P14时，注射CNTF的肌肉中近40%的纤维仍有多神经元支配，这是9天时预期的量。这些结果表明，bFGF和CNTF对发育中的神经肌肉突触都有强大而持久的影响。
