q&more
My watch list
my.chemie.de  
Login  

News

New insights into how your brain keeps its balance

Division of Life Science, HKUST

Three-color wide-field (Upper Left) and super-resolution localization microscopy (SRLM) (Upper Right) images of cultured cortical neurons labeled with anti-ATM (blue), anti-VAMP2 (green), and anti-ATR (red) antibodies. (Scale bars: as marked.)

23-Jan-2018: As with all things in life, healthy brain function depends on a balance of forces. We think of our brains as active - moving a leg and saying a word are all "active" events. But it is just as important for our brains to be able to stop these actions -to stop our leg, and to stop our speech. But how do our brains actually perform the go/stop function?

In a recent study, an interdisciplinary team of scientists from The Hong Kong University of Science and Technology (HKUST) and The Chinese University of Hong Kong (CUHK) discovered that two large protein kinases, ATM and ATR, cooperate to help establish the go/stop balance.

"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. "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." Just as important, the team found that the two proteins divide up responsibilities for the 'go' and 'stop' functions. 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 - the gap between two neurons that regulates information flow in the brain.

Utilizing super-resolution microscopy offered by the Super-Resolution Imaging Center (SRIC) at HKUST, the researchers were able to view the cellular location of the two kinases at ultra-high magnification. The custom designed super-resolution microscope with active stage locking provided the stability needed to obtain high-resolution images. The groups had previously worked together to show that ATM was found on synaptic vesicles, but no one had ever looked for ATR. Combining their efforts for a second time, the team was able to show that ATR was also on synaptic vesicles (identified with a protein called VAMP2).

"One of the challenges we faced was that even at high magnification, all vesicles look pretty much alike," said Du Shengwang, physics professor and Associate Director of SRIC. "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 VAMP2-containing synaptic vesicle."

The HKUST team then sent their findings to their collaborators at CUHK, where they produced crisp, high-resolution images of normal synapses and synapses from neurons that had no ATM protein. This allowed Cheng to measure the size of the synaptic vesicles, and she discovered that the vesicles without ATM were bigger than normal, a hint that there was a problem with the composition of the synaptic membrane.

"The new findings are in the realm of basic research, but they have important implications for human disease," said Karl Herrup, Chair Professor and Head of the Division of Life Science at HKUST, Director of the SRIC and the senior author of the manuscript. "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. This means that there is a yin-yang relationship between ATM and ATR. And really, this is only the beginning. We believe that our work has potential relevance to a much broader range of neurologic conditions."

Original publication:
Aifang Cheng, Teng Zhao, Kai-Hei Tse, Hei-Man Chow, Yong Cui, Liwen Jiang, Shengwang Du, Michael M. T. Loy, and Karl Herrup; "ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations"; PNAS; 2018

Facts, background information, dossiers

  • Hong Kong University
  • brain
  • vesicles
  • synapses
  • protein kinases
  • proteins
  • neurons
  • kinases
  • imaging

More about Hong Kong University of Science and Technology

  • q&more articles

    Fit and healthy to 120

    I turned 63 recently. My secret to staying optimistic as you age towards your inevitable death? “The idea is to die young, but as late as humanly possible…” A noble aim, indeed… more

  • Authors

    Jan Engels

    Jan Engels, born 1989, studied bio engineering at the University of Applied Sciences Aachen. After acquiring his Bachelor's degree, Prof. Reinhard Renneberg suggested him for the fast-track programme of the Hong Kong University of Science and Technology (HKUST) for a directly subsequent PhD ... more

    Prof. Dr. Reinhard Renneberg

    Reinhard Renneberg, born 1951, studied chemistry at the Lomonossov university in Moscow. After acquiring his diploma, he worked at the Zentralinstitut für Molekularbiologie (ZIM) in Berlin-Buch, where he acquired his doctorate in 1978 and habilitation in the area of bio sensors in 1991. Fro ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by:



Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE