%0 Journal Article
%T Phosphorylation of pyruvate dehydrogenase inversely associates with neuronal activity.
%A Yang D
%A Wang Y
%A Qi T
%A Zhang X
%A Shen L
%A Ma J
%A Pang Z
%A Lal NK
%A McClatchy DB
%A Seradj SH
%A Leung VH
%A Wang K
%A Xie Y
%A Polli FS
%A Maximov A
%A Gonzalez OC
%A de Lecea L
%A Cline HT
%A Augustine V
%A Yates JR
%A Ye L
%J Neuron
%V 112
%N 6
%D 2024 Mar 20
%M 38266644
%F 18.688
%R 10.1016/j.neuron.2023.12.015
%X For decades, the expression of immediate early genes (IEGs) such as 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. 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. In in vivo mouse models, monoclonal antibody-based pPDH immunostaining detected activity decreases across the brain, which were induced by a wide range of factors including general anesthesia, chemogenetic inhibition, sensory experiences, and natural behaviors. Thus, as an inverse activity marker (IAM) in vivo, 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.