PREreviews of “Phosphorylation of pyruvate dehydrogenase marks the inhibition ofin vivoneuronal activity”

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Phosphorylation of pyruvate dehydrogenase marks the inhibition ofin vivoneuronal activity

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-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.

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PREreview by Christian Macdonald et al.

Authored by Christian Macdonald, James Fraser, Zhengya Liu, and Catherine Shin

This review arose out of a course for graduate students in the life sciences at UCSF, “Peer Review in the Life Sciences,” which aims to introduce junior scientists to peer review in a critical yet constructive way. The students selected preprints to review, led discussions of them, drafted…

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PREreviews of Phosphorylation of pyruvate dehydrogenase marks the inhibition ofin vivoneuronal activity

1 PREreview