Extrasynaptic GABA(A) receptors and tonic inhibition in rat auditory thalamus.

Abstract

Neural inhibition plays an important role in auditory processing and attentional gating. Extrasynaptic GABA(A) receptors (GABA(A)R), containing α(4)and δ GABA(A)R subunits, are thought to be activated by GABA spillover outside of the synapse following release resulting in a tonic inhibitory Cl(-) current which could account for up to 90% of total inhibition in visual and somatosensory thalamus. However, the presence of this unique type of inhibition has not been identified in auditory thalamus. The present study used gaboxadol, a partially selective potent agonist for δ-subunit containing GABA(A) receptor constructs to elucidate the presence of extrasynaptic GABA(A)Rs using both a quantitative receptor binding assay and patch-clamp electrophysiology in thalamic brain slices. Intense [(3)H]gaboxadol binding was found to be localized to the MGB while whole cell recordings from MGB neurons in the presence of gaboxadol demonstrated the expression of δ-subunit containing GABA(A)Rs capable of mediating a tonic inhibitory Cl(-) current. Potent tonic inhibitory GABA(A)R responses mediated by extrasynaptic receptors may be important in understanding how acoustic information is processed by auditory thalamic neurons as it ascends to auditory cortex. In addition to affecting cellular behavior and possibly neurotransmission, functional extrasynaptic δ-subunit containing GABA(A)Rs may represent a novel pharmacological target for the treatment of auditory pathologies including temporal processing disorders or tinnitus.