Motoneurons axotomized by peripheral nerve injuries experience profound changes in their synaptic inputs that are associated with a neuroinflammatory response that includes local microglia and astrocytes. This reaction is conserved across different types of motoneurons, injuries, and species, but also displays many unique features in each particular case. These reactions have been amply studied, but there is still a lack of knowledge on their functional significance and mechanisms. In this review article, we compiled data from many different fields to generate a comprehensive conceptual framework to best interpret past data and spawn new hypotheses and research. We propose that synaptic plasticity around axotomized motoneurons should be divided into two distinct processes. First, a rapid cell-autonomous, microglia-independent shedding of synapses from motoneuron cell bodies and proximal dendrites that is reversible after muscle reinnervation. Second, a slower mechanism that is microglia-dependent and permanently alters spinal cord circuitry by fully eliminating from the ventral horn the axon collaterals of peripherally injured and regenerating sensory Ia afferent proprioceptors. This removes this input from cell bodies and throughout the dendritic tree of axotomized motoneurons as well as from many other spinal neurons, thus reconfiguring ventral horn motor circuitries to function after regeneration without direct sensory feedback from muscle. This process is modulated by injury severity, suggesting a correlation with poor regeneration specificity due to sensory and motor axons targeting errors in the periphery that likely render Ia afferent connectivity in the ventral horn nonadaptive. In contrast, reversible synaptic changes on the cell bodies occur only while motoneurons are regenerating. This cell-autonomous process displays unique features according to motoneuron type and modulation by local microglia and astrocytes and generally results in a transient reduction of fast synaptic activity that is probably replaced by embryonic-like slow GABA depolarizations, proposed to relate to regenerative mechanisms.

中文翻译：

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轴突切开术后对动子神经元的突触可塑性：范式的必要改变。

被周围神经损伤轴突切除的动子素在突触输入中发生深刻的变化，这些变化与包括局部小胶质细胞和星形胶质细胞在内的神经炎症反应有关。该反应在不同类型的运动神经元，损伤和物种中均得到保守，但在每种情况下也表现出许多独特的特征。已经对这些反应进行了充分的研究，但是仍然缺乏关于它们的功能意义和机理的知识。在这篇评论文章中，我们汇编了来自许多不同领域的数据，以生成一个全面的概念框架，以最好地解释过去的数据并产生新的假设和研究。我们建议围绕轴突化的运动神经元的突触可塑性应分为两个不同的过程。首先，快速的细胞自治 小神经胶质细胞运动神经元后可逆的运动神经元细胞体和近端树突突触的小胶质细胞独立脱落。第二，较慢的机制是小胶质细胞依赖性的，并且通过从腹角完全消除周围受伤并再生感觉的Ia传入本体感受器的轴突侧支来永久改变脊髓电路。这从细胞体和整个轴突化运动神经元的树突状树以及许多其他脊髓神经元中消除了这种输入，从而重新配置了腹角运动回路，使其在再生后起作用，而没有来自肌肉的直接感觉反馈。此过程受伤害严重程度的调节，提示由于感觉和运动轴突靶向周围错误而导致再生特异性差，这可能导致Ia传入腹侧角不适应。相反，仅当运动神经元再生时，细胞体上发生可逆的突触变化。这种细胞自主过程根据运动神经元的类型和局部小胶质细胞和星形胶质细胞的调节而显示出独特的特征，并且通常导致快速突触活性的瞬时降低，其可能被胚胎样的慢GABA去极化替代，提议与再生机制有关。