Please use this identifier to cite or link to this item:
https://www.um.edu.mt/library/oar/handle/123456789/90574
Title: | Gain-of-function of thalamic extrasynaptic GABA-A receptors in typical absence seizures |
Other Titles: | Extrasynaptic GABAA receptors |
Authors: | Crunelli, Vincenzo Di Giovanni, Giuseppe Parri, H. Rheinallt Errington, Adam C. |
Keywords: | Thalamus GABA -- Receptors GABA -- Physiological effect Dopamine Seizures Neural transmission -- Regulation |
Issue Date: | 2014 |
Publisher: | Springer |
Citation: | Crunelli, V., Di Giovanni, G., Parri, H. R., & Errington, A. C. (2014). Gain-of-function of thalamic extrasynaptic GABA-A receptors in typical absence seizures. In: A. C. Errington, G. Di Giovanni, & V. Crunelli (eds.), Extrasynaptic GABAA Receptors (pp. 223-237). New York: Springer. |
Abstract: | Epilepsy is generally viewed as resulting from an unbalanced excitatory/inhibitory drive, where either excitatory transmission is enhanced and/or inhibitory transmission is decreased. However, studies in genetic and pharmacological models of non-convulsive typical absence seizures have revealed that an increased activation of extrasynaptic γ-aminobutyric acidA (GABAA) receptors (eGABAARs), and the resulting enhanced tonic GABAA inhibition in thalamocortical (TC) neurons, is a necessary and sufficient condition for the expression of these seizures. Importantly, in genetic absence models, the mechanism underlying eGABAAR gain of function is non-neuronal in nature as it results from a malfunction in the thalamic astrocytic GABA transporter, GAT-1. These results challenge the existing view that typical absence seizures are underpinned by a widespread loss of GABAergic function in TC circuits, and are supported by the evidence that drugs that increase GABAergic signalling elicit or aggravate absence seizures in animal model and humans. Furthermore, by highlighting a vital role for astrocytes and eGABAARs in the pathophysiology of typical absence epilepsy, these new findings offer novel targets for the development of more effective anti-absence drugs. |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/90574 |
Appears in Collections: | Scholarly Works - FacM&SPB |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Gain-of-function of thalamic extrasynaptic GABA-A receptors in typical absence seizures.pdf Restricted Access | 1.29 MB | Adobe PDF | View/Open Request a copy |
Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.