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Publication : Phosphorylation of pyruvate dehydrogenase inversely associates with neuronal activity.

First Author  Yang D Year  2024
Journal  Neuron Volume  112
Issue  6 Pages  959-971.e8
PubMed ID  38266644 Mgi Jnum  J:346679
Mgi Id  MGI:7614095 Doi  10.1016/j.neuron.2023.12.015
Citation  Yang D, et al. (2024) Phosphorylation of pyruvate dehydrogenase inversely associates with neuronal activity. Neuron
abstractText  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.
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