Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus?

Abstract

Cai R, Kalappa BI, Brozoski TJ, Ling LL, Caspary DM. Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus? J Neurophysiol 111: 229 -238, 2014. First published October 23, 2013 doi:10.1152/jn.00556.2013.-Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central auditory system. Sensory thalamic structures show high levels of non-desensitizing extrasynaptic GABA A receptors (GABA A Rs) and a reduction in the redundancy of coded information. The present study compared the inhibitory potency of GABA acting at GABA A Rs between the inferior colliculus (IC) and the medial geniculate body (MGB) using quantitative in vivo, in vitro, and ex vivo experimental approaches. In vivo single unit studies compared the ability of half maximal inhibitory concentrations of GABA to inhibit sound-evoked temporal responses, and found that GABA was two to three times (P Ͻ 0.01) more potent at suppressing MGB single unit responses than IC unit responses. In vitro whole cell patch-clamp slice recordings were used to demonstrate that gaboxadol, a ␦-subunit selective GABA A R agonist, was significantly more potent at evoking tonic inhibitory currents from MGB neurons than IC neurons (P Ͻ 0.01). These electrophysiological findings were supported by an in vitro receptor binding assay which used the picrotoxin analog [ 3 H]TBOB to assess binding in the GABA A R chloride channel. MGB GABA A Rs had significantly greater total open chloride channel capacity relative to GABA A Rs in IC (P Ͻ 0.05) as shown by increased total [ 3 H]TBOB binding. Finally, a comparative ex vivo measurement compared endogenous GABA levels and suggested a trend towards higher GABA concentrations in MGB than in IC. Collectively, these studies suggest that, per unit GABA, high affinity extrasynaptic and synaptic GABA A Rs confer a significant inhibitory GABA A R advantage to MGB neurons relative to IC neurons. This increased GABA sensitivity likely underpins the vital filtering role of auditory thalamus.

GABAergic inhibition shapes SAM responses in rat auditory thalamus

“…Similar to our previous report (Cai et al, 2013), Mixed units were extremely sensitive to GABA manipulation (see exemplar in Fig. 2A).…”

“…To access the left MGB, a 2X2 mm craniotomy was drilled, exposing the dorsal surface of cortex (−5.5 mm from bregma; 3.5 mm lateral from midline). MGB unit recording depth was between 4800 um to 6800 um from the surface (Paxinos and Watson, 2007, Cai et al, 2013). …”

“…Similar to Cai et al (2013), a carbon fiber electrode attached to a five-barrel iontophoretic electrode, Carbostar-6 (Kation Scientific, Minneapolis, MN), was coupled to a headstage preamplifier, Multichannel Acquisition Processor (MAP) system and PC running MAP software and Sort Client (Plexon Inc., Dallas, TX) for real-time spike sorting. A piezoelectric advancer (David Kopf Ins., Tujunga, CA) advanced the electrode into the left MGB using 70–80 dB broadband noise pips as search signal.…”

“…The balancing barrel was filled with potassium acetate (KAc, 2 M), with remaining barrels filled with γ-Aminobutyric acid (GABA, 500 mM, pH = 4.0, Sigma-Aldrich, St. Louis, MO), gabazine (SR-95531) (GBZ, 10 mM, Sigma-Aldrich, St. Louis, MO) and AP5 (100 mM, pH = 7.4). Retaining currents were set at −15 nA as previous studies (Cai et al, 2013, Duque et al, 2013). The KAc filled balancing barrel neutralizes all currents by passing current equal and opposite currents being used.…”

“…Based on the identification of high affinity GABA A Rs mediating tonic inhibitory current and enhanced GABA sensitivity in auditory thalamus (Richardson et al, 2011, Cai et al, 2013), and the findings and models by Bartlett, Wang and colleagues (Bartlett and Wang, 2007, 2011, Rabang and Bartlett, 2011, Rebang et al, 2012), the present study sought to characterize the role of GABAergic inhibition in shaping responses to SAM stimuli for commonly observed SAM-response-types seen for MGB neurons.…”