Cutting-edge tech locates brain cells’ Off Switches with precision.

January 24, 2024

In a study published in the journal Neuron, scientists at Scripps Research have developed a new technology that allows them to track when brain cells shut off after a burst of activity, a process known as inhibition. The technology, which involves measuring levels and characteristics of proteins and their modifications, provides a new way to study the normal functioning of the brain as well as how the brain’s “off switches” may go awry in diseases and disorders. According to the senior author of the study, Li Ye, it is generally agreed that the inhibition of neurons is the major way the brain regulates activity.

The scientists used optogenetics to study how brain cells change when they are actively firing compared to when they are done firing. They found that one protein, pyruvate dehydrogenase (PDH), is rapidly changed immediately after brain cells are inhibited. To shut off PDH, cells add molecular tags called phosphates to the protein. The researchers found antibodies that only recognized this inactive, phosphorylated form of PDH, and used these antibodies to measure PDH in mice that had been given anesthesia. They found that nearly the entire brain lit up with high levels of phosphorylated PDH, correctly showing how most of the brain is inactive during anesthesia.

The researchers believe that this new technology could help identify what goes wrong in brain conditions such as depression, post-traumatic stress disorder, and Alzheimer’s disease.

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