Researchers from Duke-NUS Achieve Significant Breakthrough in
Understanding Tonic Inhibition
02 November 2010
"While this is a basic science discovery, our work certainly could lead to new targets for drug discovery by establishing a molecular explanation for an important brain signalling mechanism. Hence, the study may contribute towards future clinical or commercial applications, with international impact."
Dr George Augustine, key principal investigator from the Duke-NUS Graduate Medical School Singapore
KEY PRINCIPAL INVESTIGATOR: Dr George Augustine from the Duke-NUS Graduate Medical School Singapore who led the study on "Channel-Mediated Tonic GABA Release from Glia"
A milestone study by a team of researchers from the Duke-NUS Graduate Medical School Singapore (Duke-NUS), the Korea Institute of Science & Technology (KIST) and Duke University, was published in the prestigious journal, Science (5 November 2010) as a full research article. The paper, "Channel-Mediated Tonic GABA Release from Glia", describes a very significant breakthrough in understanding an important brain signalling mechanism called tonic inhibition.
The work establishes two novel and important points about tonic inhibition, one of the main "brake" mechanisms in the brain.
First, it demonstrates that an inhibitory neurotransmitter signal called GABA is secreted via ion channels rather than through a conventional neurotransmitter secretion mechanism. This is a big surprise to the field and demonstrates a new function for ion channels. It has been known for a long time that these channels are involved in generating electrical signals in the brain (several Nobel prizes have been awarded for this). However, this is the first time it has been demonstrated that ion channels also are directly responsible for secretion of neurotransmitters in the brain.
Second, the work shows that the GABA comes not from nerve cells but from glial cells, an abundant type of brain cells whose functions are poorly understood. This was also a big surprise to the field: glia cells were not previously known to be involved in tonic inhibition and neurons were thought to be solely responsible for GABA secretion.
Said Dr George Augustine, a key principal investigator from Duke-NUS who was involved in the project: "The overall importance of the work is that GABA is the major chemical signal responsible for inhibition of nerve cells, which is known to be important for virtually every aspect of brain function. The tonic inhibition that we studied is particularly known to be involved in sleep, memory and cognition. It is also known to be impaired in epilepsy and thought to be enhanced by drinking alcohol, which may account for some of the effects observed after drinking".
He added: "Finally, it is also an important demonstration of the potential of the new Neuroscience partnership between Duke-NUS and KIST. I have great hope that the collaboration between these two institutions will enhance the research capabilities of both Singapore and Korea and will lead to great strides in our understanding of brain function and disorders."
The study was partially funded by the National Research Foundation (NRF), Singapore.
Besides Prof. Augustine and Soojung Lee of the Neuroscience and Behavioural Disorders Programme at the Duke-NUS, other authors of the paper include Bo-Eun Yoon, Soo-Jin Oh, Hyungju Park, Hee-Sup Shin and Justin Lee of the Centre for Functional Connectomics at KIST in Seoul, Korea and Ken Berglund of the Department of Neurobiology, Duke University Medical Centre, Durham, NC, USA.
By Duke-NUS Graduate Medical School Communications Office