The general anaesthetic etomidate inhibits the excitability of mouse thalamocortical relay neurons by modulating multiple modes of GABAA receptor-mediated inhibition.
Bottom Line: Modulation of thalamocortical (TC) relay neuron function has been implicated in the sedative and hypnotic effects of general anaesthetics.Additionally, phasic inhibition evoked by stimulation of the nucleus reticularis exhibited a spillover component mediated by δ-GABAA Rs, which was significantly prolonged in the presence of etomidate.Collectively, these results suggest that the deactivation of thalamus observed during etomidate-induced anaesthesia involves potentiation of tonic and phasic inhibition, and implicate amplification of spillover inhibition as a novel mechanism to regulate the gating of sensory information through the thalamus during anaesthetic states.
Affiliation: Division of Neuroscience, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.Show MeSH
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Mentions: For current-clamp experiments investigating the effect of etomidate on VB neuron excitability, input–output curves were constructed by plotting the number of action potentials generated as a function of stimulus amplitude. To quantify etomidate-induced shifts in input–output curves, data were fit with a Boltzman sigmoidal curve according to the equation y(x) = Nmax/1 + e(X – X50)/S + Nmax), where Nmax is the number of action potentials generated at the maximum stimulus amplitude (in this case 300 pA), X is the stimulus amplitude, X50 is the stimulus amplitude producing half-maximal spike output (hereafter ‘EA50’) and S is the slope factor. For experiments investigating the effect of eIPSPs on tonic spike trains, inter-spike intervals (ISIs) were measured throughout the spike train. For baseline measurements, ISIs were determined for a 5-s period preceding each eIPSP (minimum of three stimulations) to ensure spike rates recovered to stable frequencies following inhibition. The ISI during an IPSP was simply the interval between the final spike prior to delivery of an eIPSP and the first spike following recovery from inhibition. The transient suppression of tonic spike activity induced by an eIPSP was observed as an immediate and obvious increase in the ISI (see Figs2 and 3).
Affiliation: Division of Neuroscience, Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.