May 24, 2024

New Technology Enables Tracking of Brain Cells’ Inhibition Process

Researchers at Scripps Research have developed a groundbreaking technology that allows them to track when brain cells turn off, a process known as inhibition. This development provides scientists with a new way to study the normal functioning of the brain, as well as how the brain’s off switches may malfunction in various diseases and disorders.

For years, scientists have focused on studying when different groups of brain cells activate, but understanding when these neurons deactivate is just as crucial. The recently published study in the journal Neuron presents a technique that enables researchers to monitor the shutdown of brain cells after a burst of activity.

By utilizing optogenetics, a method that controls cells’ activity through light, the scientists were able to repeatedly activate and inhibit the cells. They then measured the levels and characteristics of different proteins and their modifications. The researchers discovered that a particular protein called pyruvate dehydrogenase (PDH) underwent rapid changes immediately after brain cells were inhibited.

According to senior author Li Ye, the inhibition of neurons is a primary method by which the brain regulates its activity. However, few effective approaches for tracking inhibition have been developed until now. Ye and his team found that the brain rapidly shuts off the PDH protein once the cell is done firing.

The PDH protein is crucial for energy production when neurons are firing, as firing requires a considerable amount of energy. Nevertheless, the brain aims to conserve energy, leading to the rapid shutdown of the PDH protein after firing ceases. This process occurs much faster than other observed changes in gene expression.

To deactivate PDH, the cells add phosphates, molecular tags, to the protein. The researchers identified antibodies that specifically recognized this inactive, phosphorylated form of PDH—which they referred to as pPDH. By measuring the levels of pPDH using these antibodies, the researchers were able to determine brain cell inhibition.

To test the validity of pPDH as an indicator of brain cell inhibition, the team studied mice that had been given anesthesia. The results showed high levels of pPDH throughout the majority of the brain, accurately indicating the brain’s inactivity during anesthesia.

In another experiment, the researchers exposed animals to bright light that was then abruptly turned off. The brain cells responsible for vision, located in the visual cortex, exhibited low levels of pPDH when exposed to light, as the active form of PDH is required for signaling energy. However, immediately after the light was turned off, levels of phosphorylated protein significantly increased.

This technology represents a major breakthrough in understanding the brain’s regulation of activity and identifying potential malfunctions in various diseases and disorders, including depression, post-traumatic stress disorder, and Alzheimer’s disease. The ability to track brain cell inhibition provides scientists with valuable insights into the workings of the brain and paves the way for future research and therapeutic interventions.

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