Inhibitory brain dynamics for adaptive behaviour

Efficient brain network computations rely on suppressing cell excitation—a process known as inhibition that involves neurotransmitter activity. GABA is the primary inhibitory neurotransmitter in the brain and is known to play a key role in learning and brain plasticity. Yet, our understanding of the role of GABA in regulating the brain network dynamics that support learning has been hampered by technology limitations and a fundamental disconnect between work in animal models and humans. To tackle this challenge, we propose an integrated work programme that bridges across species (mice, humans) and scales (local circuits, global networks). We will a) match behavioural training protocols in humans and mice, focusing on perceptual learning, b) validate non-invasive Magnetic Resonance Spectroscopy (MRS-GABA) imaging capitalising on the precision afforded by neuroengineering tools (optical GABA sensors, electrophoretic GABA/drug delivery), c) combine GABA imaging with calcium imaging and electrophysiology to test the link between GABAergic inhibition and network activity, d) marry modelling and interventions (optogenetics, neuropharmacology) to test the mechanistic functions of inhibitory brain networks. Our work programme will 1) advance understanding of the inhibitory brain dynamics that mediate learning across species, 2) decipher the origins of MRS-GABA, 3) optimise GABA imaging, enhancing potential for clinical translation.