Phosphorylation of pyruvate dehydrogenase inversely associates with neuronal activity, 2024, Dong Yang et al

Highlights

• 
  
• Establishing an optogenetic-based quantitative proteomic screening platform
• Unbiased screening identified that neural activity decreases pPDH
• pPDH level negatively correlates with neural activity in vitro and in vivo
• pPDH as a novel inverse activity marker (IAM) to track reduced neuronal activity
  

Summary
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.

https://www.cell.com/neuron/fulltext/S0896-6273(23)00974-1?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S0896627323009741?showall=true

 

Novel Technology Track Brain Cells' "off switches"

Scientists have been studying for decades the activity patterns in human and animal brains by observing when different groups of brain cells turn on. However, knowing how long neurons stay active and when they turn off again have remained a mystery. Now, scientists at Scripps Research have developed a new technology that lets them track when, after a burst of activity, brain cells shut off—a process known as inhibition. Their technique, provides a new way to study not only the normal functioning of the brain, but how the brain’s “off switches” may go awry in normal behaviors as well as in diseases and disorders.

https://www.genengnews.com/topics/t...l-technology-tracks-brain-cells-off-switches/