Dhawan Serene, Myers Philip, Bailey David M D, Ostrovsky Aaron D, Evers Jan Felix, Landgraf Matthias
Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
Neural Circuits and Evolution Laboratory, The Francis Crick Institute, London, United Kingdom.
Front Cell Neurosci. 2021 Jul 5;15:641802. doi: 10.3389/fncel.2021.641802. eCollection 2021.
Neurons utilize plasticity of dendritic arbors as part of a larger suite of adaptive plasticity mechanisms. This explicitly manifests with motoneurons in the embryo and larva, where dendritic arbors are exclusively postsynaptic and are used as homeostatic devices, compensating for changes in synaptic input through adapting their growth and connectivity. We recently identified reactive oxygen species (ROS) as novel plasticity signals instrumental in this form of dendritic adjustment. ROS correlate with levels of neuronal activity and negatively regulate dendritic arbor size. Here, we investigated NADPH oxidases as potential sources of such activity-regulated ROS and implicate Dual Oxidase (but not Nox), which generates hydrogen peroxide extracellularly. We further show that the aquaporins Bib and Drip, but not Prip, are required for activity-regulated ROS-mediated adjustments of dendritic arbor size in motoneurons. These results suggest a model whereby neuronal activity leads to activation of the NADPH oxidase Dual Oxidase, which generates hydrogen peroxide at the extracellular face; aquaporins might then act as conduits that are necessary for these extracellular ROS to be channeled back into the cell where they negatively regulate dendritic arbor size.
神经元利用树突分支的可塑性，作为更大一套适应性可塑性机制的一部分。这在胚胎和幼虫的运动神经元中表现得尤为明显，在那里树突分支完全是突触后结构，并被用作稳态装置，通过调整其生长和连接性来补偿突触输入的变化。我们最近发现活性氧（ROS）是这种树突调整形式中起作用的新型可塑性信号。ROS与神经元活动水平相关，并负向调节树突分支大小。在这里，我们研究了NADPH氧化酶作为这种活动调节的ROS的潜在来源，并发现双氧化酶（而非Nox）参与其中，双氧化酶在细胞外产生过氧化氢。我们进一步表明，水通道蛋白Bib和Drip（而非Prip）是运动神经元中活动调节的ROS介导的树突分支大小调整所必需的。这些结果提示了一种模型，即神经元活动导致NADPH氧化酶双氧化酶的激活，双氧化酶在细胞外表面产生过氧化氢；然后水通道蛋白可能作为通道，使这些细胞外ROS能够回到细胞内，在那里它们负向调节树突分支大小。
