Scientists at Scripps Research Make Breakthrough in Brain Cell Study.
For many years, scientists have been watching how brain cells in humans and animals light up and turn on. But one big puzzle has been figuring out how long these neurons stay active and when they switch off. Now, a team at Scripps Research has made a big leap forward. They’ve come up with a new way to track when brain cells turn off after being active. This process, called inhibition, is crucial to understanding the brain.
Li Ye, PhD, a professor at Scripps Research, explained that stopping neuron activity is a key way the brain controls what it does. Until now, tracking this ‘off switch’ of the brain cells has been tough. But Ye and his colleague, John Yates, a professor of molecular medicine, are changing that.
They studied brain cells when they were active (sending electrical messages) and when they stopped. They used a technique called optogenetics and looked at different proteins and how they change. They found that a protein called pyruvate dehydrogenase (PDH) changes very fast when brain cells stop being active.
Ye said that PDH is part of how neurons get energy to fire. But the brain likes to save energy, so as soon as a cell stops firing, PDH is quickly shut off. This happens faster than any other changes they’ve seen in genes.
To turn off PDH, cells add something called phosphates to it. Ye’s team found special antibodies that can spot this inactive form of PDH (pPDH). They tested this idea in mice given anesthesia. They found high levels of pPDH all over the brain, showing that most brain cells are not active under anesthesia.
Ye thinks this new method can answer many questions. For example, what happens if the brain can’t turn cells off properly? Or if they stop too fast or too slow? How does this play a role in different diseases?
The team is still refining how they use pPDH, but other scientists are already using this approach. The antibodies for measuring pPDH are out there for anyone to use. This breakthrough could help figure out what goes wrong in various brain conditions like depression, PTSD, and Alzheimer’s disease.