Dynamics of the fragile X mental retardation protein correlates with cellular and synaptic properties in primary auditory neurons following afferent deprivation.
Dynamics of the fragile X mental retardation protein correlates with cellular and synaptic properties in primary auditory neurons following afferent deprivation.
复制标题
脆性X智力低下蛋白的动力学与传入剥夺后初级听觉神经元的细胞和突触特性相关。
DOI：
10.1002/cne.24959
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yu X;Wang X;Sakano H;Zorio DAR;Wang Y
传入活动动态地调节中枢神经系统中神经元的属性和连接。脆性X智力低下蛋白(FMRP)是一种RNA结合蛋白，以活性依赖的方式调节细胞和突触的特性。FMRP水平和定位是否以及如何受到传入输入的调节仍然是鲜见的研究，以及这种调节如何与神经元对感觉输入变化的反应有关尚不清楚。我们描述了FMRP水平和定位的变化，在鸡的大细胞核(NM)，一个主要的耳蜗核，在传入剥夺后，单侧耳蜗耳。我们观察到FMRP免疫反应在去传入的NM神经元的一个子集中迅速聚集成大颗粒结构。在12-24小时表现出持续的FMRP聚集的神经元最终失去了胞浆中的尼氏物质，表明细胞死亡。一周后，存活神经元中FMRP的表达恢复动态平衡，免疫染色强度略有降低，异质性增强。在稳态状态下(7-14天)的相关分析表明，FMRP表达相对较多的神经元具有更高的维持胞体大小和核糖体活性的能力，以及更好地分离不活跃的突触前终末的能力。此外，去传入后突触后抑制性蛋白GePhyrin的强度降低，并与FMRP强度呈正相关，提示FMRP参与了突触动力学对减少的传入输入的反应。总之，这项研究表明，传入输入通过与多种类型的神经元反应和突触重排相关的方式调节FMRP的表达和定位。脆性X智力低下蛋白(FMRP)以一种活性依赖的方式调节细胞和突触的特性。使用单侧耳蜗摘除作为剥夺鸡耳蜗神经元传入输入的方法，我们在经历细胞死亡的神经元子集中发现了持续的FMRP聚集。此外，我们发现在存活的神经元恢复内稳态后，FMRP水平与细胞和突触重排的新出现或增强的相关性。这些结果表明，传入信息通过与多种类型的神经元反应和突触动力学相关的方式调节FMRP的表达和定位。
Afferent activity dynamically regulates neuronal properties and connectivity in the central nervous system. The Fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates cellular and synaptic properties in an activity-dependent manner. Whether and how FMRP level and localization are regulated by afferent input remains sparsely examined and how such regulation is associated with neuronal response to changes in sensory input is unknown. We characterized changes in FMRP level and localization in the chicken nucleus magnocellularis (NM), a primary cochlear nucleus, following afferent deprivation by unilateral cochlea removal. We observed rapid (within 2 hours) aggregation of FMRP immunoreactivity into large granular structures in a subset of deafferented NM neurons. Neurons that exhibited persistent FMRP aggregation at 12–24 hours eventually lost cytoplasmic Nissl substance, indicating cell death. A week later, FMRP expression in surviving neurons regained its homeostasis, with a slightly reduced immunostaining intensity and enhanced heterogeneity. Correlation analyses under the homeostatic status (7–14 days) revealed that neurons expressing relatively more FMRP had a higher capability of maintaining cell body size and ribosomal activity, as well as a better ability to detach inactive presynaptic terminals. Additionally, the intensity of an inhibitory postsynaptic protein, gephyrin, was reduced following deafferentation and was positively correlated with FMRP intensity, implicating an involvement of FMRP in synaptic dynamics in response to reduced afferent inputs. Collectively, this study demonstrates that afferent input regulates FMRP expression and localization in ways associated with multiple types of neuronal responses and synaptic rearrangements. Fragile X mental retardation protein (FMRP) regulates cellular and synaptic properties in an activity-dependent manner. Using unilateral cochlea removal as a method to deprive afferent input to the chicken cochlear neurons, we identified a persistent FMRP aggregation in a subset of neurons that undergo cell death. In addition, we found newly emerged or enhanced correlations of FMRP level with cellular and synaptic rearrangements in the surviving neurons after regaining their homeostasis. These results demonstrate that afferent input regulates FMRP expression and localization in ways associated with multiple types of neuronal responses and synaptic dynamics.
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作者：
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通讯作者：
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