In a nutshell: A common neurotransmitter thought to inhibit cell signalling in the brain can also excite certain types of cells.

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Our brains are constantly processing information – such as what we see, hear, or smell – and finding the appropriate response. Brains do this by converting information into an electrical signal, which is transmitted from cell to cell. Everything we do – from sensing our environment, to thinking and then acting – relies on these signals travelling to the right locations in the brain at the right time.

The transmission of signals around the brain is controlled by neurotransmitters. Each brain cell usually has only one type of neurotransmitter – either excitatory or inhibitory. Excitatory neurotransmitters help to spread the electrical signal to other brain cells, whereas inhibitory neurotransmitters stop it from going further.

One of the main inhibitory neurotransmitters in the adult mammal brain is gamma-aminobutyric acid (GABA). Because of the way the brain changes from birth to adulthood, GABA was believed to have excitatory activity in the developing brain before becoming completely inhibitory in the mature brain.

But research from the Brain Function CoE is challenging that view. PhD student Dr Alex Bryson and his supervisor, Professor Steven Petrou from the Florey Institute of Neuroscience and Mental Health, have shown that even in adulthood, GABA can act as both an inhibitory and an excitatory neurotransmitter.

Together with colleagues at the University of Melbourne, they collaborated with researchers from the Blue Brain Project – a Swiss research initiative that aims to build digital reconstructions and simulations of the rodent brain using supercomputers.

Using computer models from the Blue Brain Project, they predicted that GABA might have both inhibitory and excitatory properties. By carrying out lab experiments in adult mice, the researchers confirmed that GABA can, in fact, excite certain types of brain cell.

This unexpected discovery reveals that GABA is more complicated than previously thought. It also gives researchers clues as to how the brain finds the right balance between excitation and inhibition – and how imbalances could potentially be treated.

Next steps:
The researchers plan to explore how different types of brain cells regulate excitatory activity within brain networks. In particular, they want to know how dysfunction of these mechanisms leads to brain disorders such as epilepsy.

Bryson, A., Hatch, R. J., Zandt, B.-J., Rossert, C., Berkovic, S. F., Reid, C. A., Grayden, D. B., Hill, S. L., & Petrou, S. (2020). GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons. Proceedings of the National Academy of Sciences USA, 117(6), 3192-3202. doi: 10.1073/pnas.1906369117

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