Synaptic scaling is a form of homeostatic plasticity which allows neurons to adjust their action potential firing rate in response to chronic alterations in neural activity. Synaptic scaling requires profound changes in gene expression, but the relative contribution of local and cell-wide mechanisms is controversial. Here we perform a comprehensive multi-omics characterization of the somatic and process compartments of primary rat hippocampal neurons during synaptic scaling. We uncover both highly compartment-specific and correlating changes in the neuronal transcriptome and proteome. Whereas downregulation of crucial regulators of neuronal excitability occurs primarily in the somatic compartment, structural components of excitatory postsynapses are mostly downregulated in processes. Local inhibition of protein synthesis in processes during scaling is confirmed for candidate synaptic proteins. Motif analysis further suggests an important role for trans-acting post-transcriptional regulators, including RNA-binding proteins and microRNAs, in the local regulation of the corresponding mRNAs. Altogether, our study indicates that, during synaptic scaling, compartmentalized gene expression changes might co-exist with neuron-wide mechanisms to allow synaptic computation and homeostasis.

中文翻译：

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稳态突触缩放过程中基因表达的普遍区室特异性调节

突触缩放是一种稳态可塑性，它允许神经元调整其动作电位放电率以响应神经活动的慢性变化。突触缩放需要基因表达的深刻变化，但局部和全细胞机制的相对贡献是有争议的。在这里，我们在突触缩放过程中对原代大鼠海马神经元的体细胞和过程区室进行了全面的多组学表征。我们发现了神经元转录组和蛋白质组中高度区室特异性和相关的变化。尽管神经元兴奋性的关键调节因子的下调主要发生在体细胞区室中，但兴奋性突触后的结构成分大多在过程中下调。候选突触蛋白证实了缩放过程中蛋白质合成的局部抑制。基序分析进一步表明反式转录后调节因子（包括 RNA 结合蛋白和微 RNA）在相应 mRNA 的局部调节中发挥重要作用。总而言之，我们的研究表明，在突触缩放期间，分隔的基因表达变化可能与神经元范围的机制共存，以实现突触计算和体内平衡。