Delta-containing extrasynaptic gamma-aminobutyric acid type A receptor (δ-GABAAR)

Delta-containing extrasynaptic gamma-aminobutyric acid type A receptors (δ-GABAARs) are a specialized subclass of ionotropic GABA receptors located outside the synaptic cleft, primarily in brain regions such as the hippocampus, thalamus, and cerebellum (Brickley & Mody, 2012). Unlike synaptic receptors that mediate rapid, phasic inhibition, δ-containing receptors respond to low concentrations of ambient GABA to provide a persistent, 'tonic' inhibitory current that regulates the overall excitability and 'tone' of neurons (Belelli & Lambert, 2005). These receptors are typically composed of α4βδ or α6βδ subunits and are uniquely sensitive to endogenous neurosteroids, which act as potent positive allosteric modulators (Maguire & Mody, 2008). Dysregulation of δ-GABAAR expression is strongly linked to the pathophysiology of postpartum depression and epilepsy, where fluctuations in neurosteroid levels fail to be compensated by receptor plasticity (Walton & Maguire, 2019). Therapeutic targeting of these receptors with synthetic neurosteroids like brexanolone and zuranolone has proven effective in rapidly alleviating depressive symptoms by enhancing tonic inhibitory signaling (Gunduz-Bruce et al., 2019).

Other names

Extrasynaptic GABAA receptorDelta-subunit-containing GABAA receptorTonic GABAA receptorGABRD-containing receptorδ-GABAR

Positive allosteric modulation of the GABA-A receptor chloride channel, increasing the frequency and/or duration of channel opening in response to GABA, and direct agonism at higher concentrations (Belelli & Lambert, 2005; Maguire & Mody, 2008).