The Yin And Yang Of Balance In The Brain

Scientists in Hong Kong have identified two proteins that are involved in maintaining the balance between excitation and inhibition in the brain.

AsianScientist (Feb. 2, 2018) – A team of researchers in Hong Kong has identified a mechanism that controls the activation and inhibition of brain signals. Their findings are published in the Proceedings of the National Academy of Sciences.

Moving a leg and saying a word are considered ‘active’ events initiated by the brain. But it is just as important for our brains to be able to stop these actions. The question of how our brains actually perform this go/stop function has confounded scientists for decades.

In the present study, an interdisciplinary team of scientists at the Hong Kong University of Science and Technology (HKUST) and the Chinese University of Hong Kong (CUHK) discovered that two proteins, known as ATM and ATR, cooperate to help establish the excitation and inhibition (E/I) balance in the brain.

The researchers showed that ATM and ATR regulate each other’s levels—when ATM levels drop, ATR levels increase and vice-versa. They also demonstrated that the levels of the two proteins are affected by brain activity, which means that neuronal activity and the two kinases are in a dynamic ‘conversation’ that helps to keep the appropriate E/I balance.

Furthermore, the team found that ATM helps regulate only excitatory events, while ATR helps regulate only the inhibitory ones. This is achieved by controlling the movement of tiny synaptic vesicles in the neuronal synapse, which is the gap between two neurons.

Using super-resolution microscopy offered by the Super-Resolution Imaging Center at HKUST, the researchers were able to view the cellular location of ATM and ATR at ultra-high magnification. They showed that both proteins were localized on synaptic vesicles, but would never co-exist on the same synaptic vesicle.

“One of the challenges we faced was that even at high magnification, all vesicles look pretty much alike,” said Professor Du Shengwang of HKUST. “To provide differentiation, we developed a three-color version of our super-resolution system, which allowed the team to prove that ATM and ATR were never found on the same synaptic vesicle.”

“Our findings are in the realm of basic research, but they have important implications for human disease,” said Professor Karl Herrup of HKUST. “Epilepsy, for example, is a condition where inhibition in the brain fails. As our findings would predict, humans with too little ATR suffer from epilepsy. In contrast, people with ATM deficiency are ataxic—they have a reduced ability to make finely controlled movements and keep the proper E/I ratio.

“This means that there is a yin-yang relationship between ATM and ATR… We believe that our work has potential relevance to a much broader range of neurologic conditions,” he added.

The article can be found at: Cheng et al. (2018) ATM and ATR Play Complementary Roles in the Behavior of Excitatory and Inhibitory Vesicle Populations.


Source: Hong Kong University of Science and Technology; Photo: Shutterstock.
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