One of the pleasures of working in neuroscience is that the brain never quite lets you have the simple, tidy explanation for long. A neurotransmitter that appears to do one thing often turns out to be involved in several others, depending on where it is acting, which receptors are involved, and what state the brain is in. You think you understand a system, and then the next generation of experiments shows you that the picture is more precise, more conditional and more interesting than the one you had before.
This is very much the case with GABA.
Most people who have heard of GABA know it in relation to calm. That is not wrong. GABA is the brain’s main inhibitory neurotransmitter, and without inhibition the brain could not function properly. But current research is showing us something richer than a simple calming story. GABA is involved in how the brain times itself, how it learns, how it stabilises, and how it shifts between different states.
That is why I was particularly interested in a new paper in PLOS Biology on GABA and mathematical learning [1]. It is not, you will be relieved to hear, an argument that everyone should spend more time doing algebra. The interesting point is what it tells us about learning itself.
In this study, 72 healthy young adults learned mathematical material over five days while researchers tracked brain networks and brain chemistry. The results suggest that learning may depend partly on the balance between flexibility and stability in the brain. In some people, a temporary change in GABA-related inhibition was linked with better learning. Too much stability and it may be harder to learn. Too much plasticity (the brain’s ability to re-wire its connections) and what you learn may not settle. What the study suggests is that GABA helps regulate when the brain should be open to change, and when it should hold on to what it has acquired.
That has obvious relevance beyond mathematics. Much of life depends on this same balance: learning a skill, adapting to stress, changing habits, concentrating, relaxing, even finding ease with other people. We need brains that can change, but we also need them not to change chaotically.
Another piece of work I found striking appeared in the Journal of Neuroscience, looking at a very specific GABA-A receptor subtype involved in sleep [2]. The researchers were able to observe what happened when this receptor was removed, and the important finding was that sleep did not simply become shorter as a result. Instead, the quality and organisation of sleep was disrupted. What changed was the electrical pattern of sleep itself. During REM sleep (the stage of sleep in which we dream, consolidate memories and process emotional experiences), abnormalities appeared. That is a much more interesting result than “GABA helps sleep”. It suggests that GABA is helping the sleeping brain maintain its proper organisation.
Taken together, these two studies show why GABA continues to be such an important system. It is involved in timing, rhythm, learning, memory, emotional processing and the fine control of brain activity. It helps decide when the brain should settle, when it should adapt, and when it should hold steady.
On final rather human note, another recent Journal of Neuroscience paper suggests GABA is also involved in how the brain retrieves memories of unpleasant alcohol-related experiences [3]. So even the GABA system may remember a bad night, though of course the biology is rather more complicated than that.
The science is becoming more precise. The human question remains simple enough: how do we better support the states that help us rest, learn, connect and live well?
— Professor Dave Nutt
References
[1] Zacharopoulos G, Dehghani M, Krause-Sorio B, Near J, Cohen Kadosh R. “Functional connectivity and GABAergic signaling modulate the enhancement effect of neurostimulation on mathematical learning.” PLOS Biology. 2025;23(7):e3003200.
[2] Lambert PM, Salvatore SV, Lu X, Shu H-J, Benz A, Rensing N, Yuede CM, Wong M, Zorumski CF, Mennerick S. “A Role for δ Subunit-Containing GABA-A Receptors on Parvalbumin-Positive Neurons in Maintaining Electrocortical Signatures of Sleep States.” Journal of Neuroscience. 2025;45(20):e0601242025.
[3] Taxier LR, Neira S, Flanigan ME, Haun HL, Eberle MR, Kooyman LS, Markowitz SY, Kash TL. “Retrieval of an Ethanol-Conditioned Taste Aversion Promotes GABAergic Plasticity in the Anterior Insular Cortex.” Journal of Neuroscience. 2025;45(9):e0525242024.
