ePoster

Inhibitory brain dynamics for adaptive behaviour: The role of GABAergic neurotransmission in orientation discrimination-based visual perceptual learning

Matthew Bailey, Olivia Stupart, Clara Velazquez-Sanchez, Livia Wilod Versprille, Harry Robson, Johann du Hoffmann, Zoe Kourtzi, Jeffrey Dalley
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Matthew Bailey, Olivia Stupart, Clara Velazquez-Sanchez, Livia Wilod Versprille, Harry Robson, Johann du Hoffmann, Zoe Kourtzi, Jeffrey Dalley

Abstract

Gamma-aminobutyric acid (GABA) plays a key role in learning and brain plasticity by regulating functional connectivity and oscillatory activity in local circuits and global brain networks. Altered cortical inhibition is associated with perceptual and learning impairments in psychiatric disorders such as schizophrenia. Despite the importance of GABAergic inhibition for brain function, we lack a mechanistic understanding of the inhibitory network dynamics that support adaptive behaviour from training. To unravel these mechanisms, we developed a progressive 3-stimuli touchscreen orientation discrimination task for rodents derived from the perceptual paradigm used in humans. Here, decreasing angular separation from target reduced baseline accuracy, and increased response latency in males. Based on the evidence that human resting state MRS GABA levels predict orientation-based perceptual acuity, we then investigated the impacts of systemic pharmacological potentiation of GABAergic pathways on perceptual performance. The GAT-1 inhibitor Tiagabine and GABA-B agonist R-Baclofen showed no dose-dependent effects on accuracy between specific angular separations. However, the GABA-A α5 subunit positive allosteric modulator Alogabat enhanced performance in a dose-angle-sex dependent manner. Baclofen and Alogabat also exhibited dose-dependent improvements in full-task accuracy, with high doses improving accuracy in males and low-performing animals, respectively. Together, this evidence indicates a crucial role of inhibition in visual acuity and highlights that systemic pharmacological manipulation of the GABAergic pathways with our task is suitable for modelling the inhibitory dynamics of the visual system. Application of this task to generate a universal systems model of the GABAergic component of visual perceptual learning translatable across scales is warranted.

Unique ID: fens-24/inhibitory-brain-dynamics-adaptive-behaviour-6342b9dc