GABA Neurotransmission Enhanced in Auditory Thalamus Relative to Inferior

28 GABA is the major inhibitory neurotransmitter in the central auditory system. Sensory 29 thalamic structures show high levels of non-desensitizing extrasynaptic GABAA receptors 30 (GABAARs) and a reduction in the redundancy of coded information. The present study 31 compared the inhibitory potency of GABA acting at GABAARs between the inferior 32 colliculus (IC) and the medial geniculate body (MGB) using quantitative in vivo, in vitro, 33 and ex vivo experimental approaches. In vivo single unit studies compared the ability of 34 half maximal inhibitory concentrations of GABA to inhibit sound-evoked temporal 35 responses, and found that GABA was 2-3 times (p < 0.01) more potent at suppressing 36 MGB single unit responses than IC unit responses. In vitro whole-cell patch-clamp slice 37 recordings were used to demonstrate that gaboxadol (GBX), a δ subunit selective 38 GABAAR agonist, was significantly more potent at evoking tonic inhibitory currents from 39 MGB neurons than IC neurons (p < 0.01). These electrophysiological findings were 40 supported by an in vitro receptor binding assay which used the picrotoxin analog, 41 [H]TBOB, to assess binding in the GABAAR chloride channel. MGB GABAARs had 42 significantly greater total open chloride channel capacity relative to GABAARs in IC (p < 43 0.05) as shown by increased total [H]TBOB binding. Finally, a comparative ex vivo 44 measurement compared endogenous GABA levels and suggested a trend towards 45 higher GABA concentrations in MGB than in IC. Collectively these studies suggest that, 46 per unit GABA, high affinity extrasynaptic and synaptic GABAARs confer a significant 47 inhibitory GABAAR advantage to MGB neurons relative to IC neurons. This increased 48 GABA sensitivity likely underpins the vital filtering role of auditory thalamus. 49