Steward Oswald, Yonan Jennifer M, Falk Paula M
Reeve-Irvine Research Center, University of California, Irvine, Irvine, CA, United States.
Department of Anatomy & Neurobiology, University of California, Irvine, Irvine, CA, United States.
Front Mol Neurosci. 2021 Sep 10;14:735919. doi: 10.3389/fnmol.2021.735919. eCollection 2021.
The mutation, which arose spontaneously in C57Bl/6 mice, remarkably delays the onset of Wallerian degeneration of axons. This remarkable phenotype has transformed our understanding of mechanisms contributing to survival vs. degeneration of mammalian axons after separation from their cell bodies. Although there are numerous studies of how the mutation affects axon degeneration, especially in the peripheral nervous system, less is known about how the mutation affects degeneration of CNS synapses. Here, using electron microscopy, we explore how the mutation affects synaptic terminal degeneration and withering and re-growth of dendritic spines on dentate granule cells following lesions of perforant path inputs from the entorhinal cortex. Our results reveal that substantial delays in the timing of synapse degeneration in mice are accompanied by paradoxical hypertrophy of spine heads with enlargement of post-synaptic membrane specializations (PSDs) and development of spinules. These increases in the complexity of spine morphology are similar to what is seen following induction of long-term potentiation (LTP). Robust and paradoxical spine growth suggests yet to be characterized signaling processes between amputated but non-degenerating axons and their postsynaptic targets.
这种在C57Bl/6小鼠中自发产生的突变，显著延迟了轴突华勒氏变性的发生。这一显著的表型改变了我们对哺乳动物轴突从其细胞体分离后存活与变性机制的理解。尽管有许多关于该突变如何影响轴突变性的研究，特别是在周围神经系统中，但对于该突变如何影响中枢神经系统突触的变性了解较少。在这里，我们使用电子显微镜，探究该突变如何影响突触终末变性以及在来自内嗅皮质的穿通通路输入受损后齿状颗粒细胞上树突棘的萎缩和再生。我们的结果表明，突变小鼠突触变性时间的显著延迟伴随着棘突头部的反常肥大，伴有突触后膜特化（PSD）的扩大和棘状小体的形成。棘突形态复杂性的这些增加类似于在诱导长时程增强（LTP）后所观察到的情况。强大且反常的棘突生长表明在切断但未变性的轴突与其突触后靶点之间存在尚未被表征的信号传导过程。
