GABA inhibitory neurotransmitter excites cells in the adult brain

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neurons firing close up

This illustration shows the cleft between two brain cells, where neurotransmitters control the movement of electrical signals from one cell to the other. Picture: Shutterstock

A common neurotransmitter is known to inhibit cell signalling in the adult brain. Researchers have discovered that it can also excite certain types of cells.


Read the abstract


Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter in the brain. Paradoxically, it can also act as an excitatory neurotransmitter in the brains of adult mammals. This was first observed following periods of extreme inhibitory activity that fundamentally alters the ion balance in the brain, causing GABA to excite rather than inhibit. However, new research shows that even under normal levels of activity, GABA can unexpectedly excite neurons. This discovery was made by Dr Alexander Bryson from the research team of Professor Steven Petrou. It reveals a new way in which complex brain function can emerge.

Neurotransmitters control the movement of electrical signals between brain cells. How we perceive and react to our environment relies on neurotransmitters moving signals to the right locations in the brain at the right time.

Each brain cell usually has only one type of neurotransmitter. Excitatory neurotransmitters help to spread the electrical signal to other brain cells. Inhibitory neurotransmitters stop the signal from going further.

The research team collaborated with researchers from the Blue Brain Project. This Swiss research initiative aims to build digital reconstructions and simulations of the mouse brain using supercomputers. Based on computer models from the Blue Brain Project, the team predicted that GABA might have both inhibitory and excitatory properties. Lab experiments confirmed the prediction: GABA can, in fact, excite certain types of brain cell in adult mice.

This finding 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 networks leads to brain disorders such as epilepsy.

Funding

ARC Centre of Excellence for Integrative Brain Function (CE140100007)

Publication

Bryson A et al (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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