Phosphorylation of pyruvate dehydrogenase marks the inhibition of in vivo neuronal activity.
Phosphorylation of pyruvate dehydrogenase marks the inhibition of in vivo neuronal activity.
复制标题
丙酮酸脱氢酶的磷酸化标志着体内神经元活动的抑制。
DOI：
10.1101/2023.03.13.532494
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ye,Li
中科院分区：
文献类型：
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作者：
Yang,Dong;Wang,Yu;Qi,Tianbo;Zhang,Xi;Shen,Leyao;Ma,Jingrui;Pang,Zhengyuan;Lal,NeerajK;McClatchy,DanielB;Wang,Kristina;Xie,Yi;Polli,Filip;Maximov,Anton;Augustine,Vineet;Cline,HollisT;Yates,JohnR;Ye,Li
几十年来，c-fos等即刻早期基因(IEGs)的表达一直是代表神经元活化的最广泛使用的分子标记。然而，到目前为止，还没有可用于降低神经元活动(即抑制)的同等替代品。在这里，我们开发了一种基于光遗传学的生化屏幕，其中群体神经活动可以通过单个动作电位精确的光来控制，随后是无偏的磷蛋白质组图谱。我们发现，在初级神经元中，丙酮酸脱氢酶(PPDH)的磷酸化与动作电位放电的强度呈负相关。在活体小鼠模型中，基于单抗的pPDH免疫染色检测到由包括全身麻醉、感觉体验和自然行为在内的广泛因素引起的整个大脑的神经元抑制。因此，作为神经元抑制的活体标记物，pPDH可以与IEGs或其他细胞类型标记物一起用于描述和识别由经验或行为诱导的双向神经动力学。
For decades, the expression of immediate early genes (IEGs) such as c-foshas been the most widely used molecular marker representing neuronal activation. However, to date, there is no equivalent surrogate available for the decrease of neuronal activity (i.e., inhibition). Here, we developed an optogenetic-based biochemical screen in which population neural activities can be controlled by light with single action potential precision, followed by unbiased phosphoproteomic profiling. We identified that the phosphorylation of pyruvate dehydrogenase (pPDH) inversely correlated with the intensity of action potential firing in primary neurons. Inin vivomouse models, monoclonal antibody-based pPDH immunostaining detected neuronal inhibition across the brain induced by a wide range of factors including general anesthesia, sensory experiences, and natural behaviors. Thus, as anin vivomarker for neuronal inhibition, pPDH can be used together with IEGs or other cell-type markers to profile and identify bi-directional neural dynamics induced by experiences or behaviors.