GABAA Receptor Modulation by Neurosteroids in Models of Temporal Lobe Epilepsies

The document from December 2012 reviews the impact of neurosteroids on GABA_A receptor modulation in temporal lobe epilepsies (TLE). It explains that neurosteroids act as positive allosteric modulators of GABA_A receptors, which are essential for tonic inhibition in the brain. The review indicates that in TLE, there is a down-regulation of the δ-subunit of GABA_A receptors in dentate gyrus granule cells, but tonic inhibition remains unchanged due to mediation by other subunits. Conversely, tonic inhibition in interneurons is increased and remains sensitive to neurosteroids. The document also discusses the heterogeneity of GABAergic innervation and the importance of GABA_A receptor subunit composition in TLE models. It highlights the functional relevance of tonic inhibition mediated by extrasynaptic GABA_A receptors, which is altered in TLE, and the role of chloride transporters in the pathophysiology of TLE. The review suggests that understanding the modulation of GABA_A receptors and the potential for therapeutic intervention with neurosteroids could be significant for TLE treatment, especially considering the altered response to neurosteroids in TLE and the influence of stress or hormonal changes on seizure activity.