Researchers pinpoint how the brain regulates itself

A group of international researchers has discovered two large proteins in the brain that work together in producing its ‘stop’ and ‘go’ functions, much like a children’s game of “Red Light, Green Light.”

A team of interdisciplinary researchers from the Hong Kong University of Science and Technology (HKUST) and the Chinese University of Hong Kong (CUHK) published the research online Jan. 9 in the Journal Proceedings of the National Academy of Sciences.

Super-resolution microscopy housed by the Super-Resolution Imaging Center (SRIC) at HKUST was used to view the cellular location of two large protein kinases, ATM and ATR. While the team previously demonstrated that ATM was found in areas of the brain associated with stop and go functions, no one to this point had looked at ATR.

"Our discovery offers a fresh perspective on how our brain balances excitation and inhibition—basically ‘go’ and ‘stop’ of behavior," said Aifang Cheng, first author of the paper in a public release. "We show that ATM and ATR regulate each other's levels in the brain. When ATM levels drop, ATR levels increase and the reverse. Just as important, regular brain activity also changes the levels of the two proteins. This means that neuronal activity and the two kinases are in a dynamic 'conversation' that helps to keep the appropriate balance between excitation and inhibition (known as the E/I balance) by adjusting the levels of ATM and ATR."

Researchers at HKUST sent their findings to their colleagues at CUHK, who created high-resolution images of regular synapses and synapses from neurons with no ATM protein. They were able to compare the images, finding areas of the brain without ATM were bigger than normal—a signal to researchers to closely look at distortions in the synaptic membrane.

The findings may have important implications for the study of human disease, said senior author Karl Herrup, chair professor and head of the division of life science at HKUST, in the same release.

"Epilepsy, for example, is a condition where one of the problems is that inhibition fails. As our findings would predict, humans with too little ATR have a problem with epilepsy, while people with ATM deficiency by contrast are ataxic - a reduced ability to make finely controlled movements and keep the proper E/I ratio,” Herrup said in the release.