Fundamental Neurochemistry Review: GABAA receptor neurotransmission and epilepsy: Principles, disease mechanisms and pharmacotherapy

• Published in: Journal of neurochemistry 2023-04, Vol.165 (1), p.6-28
• Main Authors: Bryson, Alexander, Reid, Christopher, Petrou, Steven
• Format: Article
• Language: English
• Subjects: Drug therapy; Epilepsy; GABA; Neural networks; Neurological diseases; Neurotransmission; Receptors; γ-Aminobutyric acid A receptors
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.15769

Epilepsy is a common neurological disorder associated with alterations of excitation‐inhibition balance within brain neuronal networks. GABAA receptor neurotransmission is the most prevalent form of inhibitory neurotransmission and is strongly implicated in both the pathophysiology and treatment of epilepsy, serving as a primary target for antiseizure medications for over a century. It is now established that GABA exerts a multifaceted influence through an array of GABAA receptor subtypes that extends far beyond simply negating excitatory activity. As the role of GABAA neurotransmission within inhibitory circuits is elaborated, this will enable the development of precision therapies that correct the network dysfunction underlying epileptic pathology. GABAA receptor neurotransmission exerts a powerful inhibitory influence upon brain neuronal networks through a diverse array of GABAA receptor subtypes. Dysfunction of GABAA receptor neurotransmission is intimately associated with the pathophysiology of epilepsy, and drugs that augment this pathway have been a mainstay of epilepsy pharmacotherapy for over a century. The heterogeneous influence of GABAA neurotransmission upon cellular and neuronal network activity presents challenges for unravelling its complex functional roles, but also future opportunities for the precise manipulation of inhibitory neural circuits to treat epilepsy.