Structure-Function Dynamics of Inhibitory Neurotransmitter Receptors in Neural Circuits and Neurological Disorders

Fast inhibitory neurotransmission in the mammalian brain and spinal cord is primarily mediated by γ-aminobutyric acid type A (GABAA) and glycine receptors, whose structural diversity, subcellular localization, and dynamic regulation are central to neuronal excitability, network stability, and plasticity. As pentameric ligand-gated chloride channels, these receptors share key architectural features yet display distinct subunit compositions, biophysical properties, and pharmacological profiles. Their precise organization and modulation at synaptic and extrasynaptic sites is essential for maintaining excitation–inhibition balance across neural circuits.Advances in structural biology, cryo-electron microscopy, super-resolution imaging, proteomics, and genetic manipulation have transformed our understanding of how inhibitory receptor architecture governs channel gating, ligand binding, trafficking, and interactions with intracellular scaffolding and signaling complexes. These approaches are revealing how receptor conformation and subunit composition are dynamically regulated by neuronal activity, developmental programs, neuromodulators, and disease-associated mutations. Growing evidence also indicates that disruptions in the structure–function relationships of GABAA and glycine receptors contribute to a broad range of neurological and neuropsychiatric conditions, including epilepsy, hyperekplexia, chronic pain, anxiety disorders, autism spectrum disorders, schizophrenia, Alzheimer’s disease, stroke, and brain tumors.This Research Topic aims to bring together studies that probe the molecular mechanisms linking inhibitory receptor structure, regulation, and function to neuronal signaling and circuit-level outcomes in health and disease. By integrating insights from molecular neuroscience, pharmacology, and systems biology, this collection seeks to clarify how receptor dynamics shape inhibitory transmission and how these pathways may be harnessed for therapeutic intervention.We welcome contributions utilizing biochemical, structural, genetic, electrophysiological, imaging, and computational approaches, including studies using genetically engineered model organisms, human-derived cells, and advanced in vitro systems. Submissions that connect molecular alterations in GABAA or glycine receptors to defined cellular, synaptic, or behavioral phenotypes are particularly encouraged. Comparative studies addressing shared or divergent mechanisms across inhibitory receptor families are also welcome.Topics of interest include, but are not limited to:• Structural determinants of GABAA and glycine receptor assembly, gating, and ligand recognition• Subunit-specific regulation, trafficking, and synaptic targeting of inhibitory receptors• Activity-dependent and signaling-mediated modulation of GABAergic and glycinergic transmission• Interactions between inhibitory receptors and intracellular scaffolding proteins, kinases, and phosphatases• Roles of inhibitory receptor plasticity in development, learning, and homeostatic regulation• Pathogenic mutations and post-translational modifications affecting receptor function• Altered inhibitory signaling in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders, as well as in motor and sensory dysfunction• Pharmacological targeting of GABAA and glycine receptor subtypes for precision therapeutics• Novel compounds, biologics, and gene-based strategies to restore inhibitory balance Topic editors: Stefania Scalise, Thomas PREVOT Source: https://www.frontiersin.org/research-topics/79212/structure-function-dynamics-of-inhibitory-neurotransmitter-receptors-in-neural-circuits-and-neurological-disorders