Evidence that a common neurotransmitter can selectively regulate the excitability of neurons has been uncovered by an international research collaboration.

The researchers were investigating gamma-aminobutyric acid, known as GABA, the primary inhibitory neurotransmitter in the human brain.

“We were using computer models from the Blue Brain Project, which predicted that GABA could be having two different functions—increasing the excitability of one type of interneuron, and decreasing the excitability of another type of interneuron. This was surprising to us because GABA is primarily thought to inhibit or reduce the excitability of neurons,"

said Dr. Alexander Bryson from the Florey Institute of Neuroscience and Mental Health.

Electrophysiological Variation

The researchers were subsequently able to observe the phenomenon in the laboratory. The results[1] challenge the prevailing scientific view. They also suggest that subtypes of interneurons defined by their electrophysiology characteristics can undergo selective modulation by GABA.

Professor Sean Hill, co-Director at the EPFL Blue Brain Project, says the results were only possible through collaboration. The team brought together modeling expertise and computational infrastructure from Blue Brain, and receptor expertise and data from the Florey Institute.

“The result was wholly counterintuitive and exciting, with significant implications for understanding brain circuit alterations in mental health disorders,"

said Professor Hill.

“Understanding the human brain is one of the great challenges remaining for scientists. GABA is the predominant chemical messenger in the brain, and we already knew its role changes over the course of neurodevelopment. These findings show additional complexity of this common neurotransmitter,"

said Professor Steven Petrou, Director of the Florey Institute.

[1] Alexander Bryson, Robert John Hatch, Bas-Jan Zandt, Christian Rossert, Samuel F. Berkovic, Christopher A. Reid, David B. Grayden, Sean L. Hill, Steven Petrou. GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons. Proceedings of the National Academy of Sciences Feb 2020, 117 (6) 3192-3202; DOI: 10.1073/pnas.1906369117

Image: Florey Institute of Neuroscience and Mental Health

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