GABAA receptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol

摘要: The neurotransmitter GABA mediates the majority of rapid inhibition in CNS. Inhibition can occur via conventional mechanism, transient activation subsynaptic GABAA receptors (GABAA-Rs), or continuous high-affinity by low concentrations ambient GABA, leading to “tonic” that control levels excitability and network activity. GABAA-R α4 subunit is expressed at high dentate gyrus thalamus suspected contribute extrasynaptic GABAA-R-mediated tonic inhibition. Mice were engineered lack targeted disruption Gabra4 gene. Subunit knockout mice are viable, breed normally, superficially indistinguishable from WT mice. In electrophysiological recordings, these show a granule cells thalamic relay neurons. Behaviorally, insensitive ataxic, sedative, analgesic effects novel hypnotic drug, gaboxadol. These data demonstrate neurons mediated GABAA-Rs containing gaboxadol achieves its this subtype.