Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons
Nerve Growth Factor Regulates the Firing Patterns and Synaptic Composition of Motoneurons
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DOI：
10.1523/jneurosci.0719-10.2010
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发表时间：
2010-06-16
影响因子：
5.3
通讯作者：
Pastor, Angel M.
中科院分区：
文献类型：
--
作者：
Davis-Lopez de Carrizosa, Maria A.;Morado-Diaz, Camilo J.;Pastor, Angel M.
靶标衍生的神经营养素在成人大脑中发挥强大的突触营养作用，并参与不同形式的突触可塑性的调节。由于缺乏营养支持，目标断开会产生严重的突触剥离。因此，目标神经支配导致突触重塑和细胞功能恢复。眼外运动神经元的独特之处在于，它们通常在成人中表达 TrkA 神经营养蛋白受体，这是其他颅或脊髓运动神经元中未见的特征，除了轴索切断术等病变或肌萎缩侧索硬化症等神经退行性疾病后。我们通过将神经生长因子（NGF）逆行递送至成年猫的外展运动神经元来研究神经生长因子（NGF）的作用。轴切术减少了体细胞的密度以及整体的强直和阶段性发射调节。 NGF 治疗恢复了轴突运动神经元的突触输入和放电调节。当酪氨酸激酶活性的选择性抑制剂 K252a 用于专门测试 TrkA 效应时，NGF 介导的突触恢复和放电相关参数被废除。然而，与对照或轴突运动神经元相比，NGF 增加了放电变异性和募集阈值。有趣的是，在应用 REX（一种针对神经营养蛋白受体 p75 (p75(NTR)) 的抗体）后，这些参数恢复正常。总之，NGF 通过 TrkA 受体逆行作用，支持传入信号并调节与眼球运动相关的爆发和紧张信号。另一方面，p75(NTR) 激活调节募集阈值，从而影响放电规律。据我们所知，这是第一份显示 NGF 对体内运动神经元强大的突触营养作用的报告。
Target-derived neurotrophins exert powerful synaptotrophic actions in the adult brain and are involved in the regulation of different forms of synaptic plasticity. Target disconnection produces a profound synaptic stripping due to the lack of trophic support. Consequently, target reinnervation leads to synaptic remodeling and restoration of cellular functions. Extraocular motoneurons are unique in that they normally express the TrkA neurotrophin receptor in the adult, a feature not seen in other cranial or spinal motoneurons, except after lesions such as axotomy or in neurodegenerative diseases like amyotrophic lateral sclerosis. We investigated the effects of nerve growth factor (NGF) by retrogradely delivering this neurotrophin to abducens motoneurons of adult cats. Axotomy reduced the density of somatic boutons and the overall tonic and phasic firing modulation. Treatment with NGF restored synaptic inputs and firing modulation in axotomized motoneurons. When K252a, a selective inhibitor of tyrosine kinase activity, was applied to specifically test TrkA effects, the NGF-mediated restoration of synapses and firing-related parameters was abolished. Discharge variability and recruitment threshold were, however, increased by NGF compared with control or axotomized motoneurons. Interestingly, these parameters returned to normal following application of REX, an antibody raised against neurotrophin receptor p75 (p75(NTR)). In conclusion, NGF, acting retrogradely through TrkA receptors, supports afferent boutons and regulates the burst and tonic signals correlated with eye movements. On the other hand, p75(NTR) activation regulates recruitment threshold, which impacts on firing regularity. To our knowledge, this is the first report showing powerful synaptotrophic effects of NGF on motoneurons in vivo.