Wang Yupu, Zhang Ruiling, Huang Sihao, Valverde Parisa Tajalli-Tehrani, Lobb-Rabe Meike, Ashley James, Venkatasubramanian Lalanti, Carrillo Robert A
Department of Molecular Genetics and Cellular Biology, University of Chicago, Chicago, IL 60637.
Neuroscience Institute, University of Chicago, Chicago, IL 60637.
bioRxiv. 2023 Apr 10:2023.04.09.536190. doi: 10.1101/2023.04.09.536190.
Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the cell death of their neighbors is not fully understood. In the larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their axon terminal size and activity. We termed this compensation as cross-neuron plasticity, and in this study, we demonstrated that the engulfment receptor, Draper, and the associated kinase, Shark, are required in glial cells. Surprisingly, overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. Synaptic plasticity normally declines as animals age, but in our system, functional cross-neuron plasticity can be induced at different time points, whereas structural cross-neuron plasticity can only be induced at early stages. Our work uncovers a novel role for glial Draper signaling in cross-neuron plasticity that may enhance nervous system function during neurodegeneration and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons.
神经元细胞死亡及随后的脑功能障碍是衰老和神经退行性变的标志，但附近的健康神经元（旁观者）如何对其邻居的细胞死亡做出反应尚不完全清楚。在幼虫神经肌肉系统中，旁观者运动神经元可以通过增加轴突终末大小和活性在结构和功能上补偿其邻居的损失。我们将这种补偿称为跨神经元可塑性，在本研究中，我们证明吞噬受体Draper和相关激酶Shark在神经胶质细胞中是必需的。令人惊讶的是，Draper-I亚型的过表达增强了跨神经元可塑性，这意味着可塑性的强度与Draper信号相关。随着动物年龄增长，突触可塑性通常会下降，但在我们的系统中，功能性跨神经元可塑性可在不同时间点诱导，而结构性跨神经元可塑性只能在早期诱导。我们的工作揭示了神经胶质Draper信号在跨神经元可塑性中的新作用，这可能在神经退行性变期间增强神经系统功能，并为健康的旁观者神经元如何应对其相邻神经元的损失提供了见解。
