Phosphorylation of pyruvate dehydrogenase marks the inhibition ofin vivo neuronal activity
Authored by
Dong Yang, Yu Wang, Tianbo Qi, Xi Zhang, Leyao Shen, Jingrui Ma, Zhengyuan Pang, Neeraj K. Lal, Daniel B. McClatchy, Kristina Wang, Yi Xie, Filip Polli, Anton Maximov, Vineet Augustine, Hollis T. Cline, John R. Yates III, and Li Ye
Posted
March 14, 2023
Server
bioRxiv
DOI
10.1101/2023.03.13.532494
Abstract
Summary For decades, the expression of immediate early genes (IEGs) such as c-fos has 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 vivo mouse 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 vivo marker 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.
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