Tonic GABAA receptor conductance in medial subnucleus of the tractus

20 We previously reported that gastric activity is controlled by a robust GABAA 21 receptor–mediated inhibition in the medial nucleus of the tractus solitarius (mNTS) 22 (Herman et al. 2009) and that μ-opioid receptor activation inhibits gastric tone by 23 suppression of this GABA signaling (Herman et al. 2010). These data raised two 24 questions: (1) whether any of this inhibition was due to tonic GABAA receptor-mediated 25 conductance in the mNTS, and (2) whether μ-opioid receptor activation suppressed 26 both tonic and phasic GABA signaling. In whole-cell recordings from rat mNTS neurons, 27 application of three GABAA receptor antagonists (gabazine, bicuculline and picrotoxin) 28 produced a persistent reduction in holding current and decrease in population variance 29 or RMS noise, suggesting a blockade of tonic GABA signaling. Application of gabazine 30 at a lower concentration abolished phasic currents but had no effect on tonic currents or 31 RMS noise. Application of the delta-subunit preferring agonist gaboxadol (THIP) 32 produced a dose-dependent persistent increase in holding current and RMS noise. 33 Pretreatment with tetrodotoxin (TTX) prevented the action of gabazine but had no effect 34 on the THIP-induced current. Membrane excitability was unaffected by the selective 35 blockade of phasic inhibition, but was increased by blockade of both phasic and tonic 36 currents. In contrast, activation of tonic currents decreased membrane excitability. 37 Application of the μ-opioid receptor agonist DAMGO produced a persistent reduction in 38 holding current that was not observed following pretreatment with a GABAA receptor 39 antagonist and was not evident in mice lacking the delta subunit. These data suggest 40 that mNTS neurons possess a robust tonic inhibition that is mediated by GABAA 41 receptors containing the delta subunit, that determines membrane excitability, and that 42 is partially regulated by μ-opioid receptors. 43