Differential effects of isoflurane on excitatory and inhibitory synaptic inputs to thalamic neurones in vivo  O. Detsch, E. Kochs, M. Siemers, B. Bromm, C. Vahle-Hinz  British Journal of Anaesthesia  Volume 89, Issue 2, Pages 294-300 (August 2002) DOI: 10.1093/bja/aef170 Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 1 Model and mathematical procedure to analyse the effects of an increase in concentration of isoflurane on excitatory and inhibitory inputs to thalamocortical relay neurones (TCNs) (adapted from 23). The response activity of TCNs was recorded under two levels of isoflurane anaesthesia (ISOlow ∼0.9%, ISOhigh ∼1.9%) with and without local blockade of GABAA receptors via iontophoretic administration of the GABAA receptor antagonist bicuculline (BIC) to the vicinity of the recorded TCN. This allows quantification of the differential changes in excitatory and inhibitory inputs to the TCN under investigation produced by the increase in concentration of isoflurane. Estimates of Δ INHIBITION and Δ EXCITATION reflect the changes in the strength of GABAAergic inhibition and glutamatergic excitation (mediated via NMDA and non-NMDA receptors), respectively. British Journal of Anaesthesia 2002 89, 294-300DOI: (10.1093/bja/aef170) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 2 Effects of isoflurane and blockade of local GABAA receptors on response activity of a single thalamocortical relay neurone (TCN). (a) Under ISOlow, 34 Hz vibration of a whisker (bottom trace) elicited spike discharges occurring phase locked to the cycles of the stimuli. Administration of the GABAA receptor antagonist bicuculline (BIC) caused an increase in response activity (see also b). The responses were essentially abolished by the increase in concentration of isoflurane (ISOhigh). Responses were re-established under ISOhigh with bicuculline iontophoresis. The initial response activity reappeared after return to ISOlow. Recovery records sampled after each drug administration are not shown. Each peristimulus time histogram is a count of action potential discharges into successive 1 ms bins, accumulated over 20 consecutive stimulus presentations. Insets show oscilloscope traces of single responses under ISOlow and ISOhigh. (b) Quantification of the effects of an increase in concentration of isoflurane on excitatory and inhibitory inputs to the TCN. The inhibitory constants α1 and α2, Δ INHIBITION and Δ EXCITATION were calculated using the response activities before and during bicuculline administration under ISOlow and ISOhigh (top) according to the equations given in Figure 1. In this neurone, the increase in concentration of isoflurane caused an enhancement of inhibitory inputs by 75% and a reduction of excitatory inputs by 29%, which concomitantly led to a reduction of the response activity by 99% (bottom). British Journal of Anaesthesia 2002 89, 294-300DOI: (10.1093/bja/aef170) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 3 (a) Population data (n=15; mean and sem) depicting the isoflurane-induced suppression of response activity (*P<0.001 vs baseline), and the enhanced response activities induced by blockade of local GABAA receptors (+bicuculline) under both the low and the high concentration of isoflurane (**P<0.001 vs respective control; †P<0.001 vs +bicuculline at ISOlow). (b) The increase in concentration of isoflurane caused an enhancement of inhibition of TCNs (reflected by a mean change in inhibition of 102%), whilst the excitatory input to TCNs was suppressed (reflected by a mean change of excitation of –54%). Both effects contributed to the resulting net suppression of TCN response activity of 86 (4)%. British Journal of Anaesthesia 2002 89, 294-300DOI: (10.1093/bja/aef170) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions