Imbalanced suppression of excitatory and inhibitory synaptic transmission onto mouse striatal projection neurons during induction of anesthesia with sevoflurane in vitro.

2012 
Abstract Suppression of movement during induction of anesthesia is mediated through subcortical structures. We studied the effects of a brief, 5-min application of a clinically relevant concentration of sevoflurane (two minimum alveolar concentration) on the electrophysiological activities of the medium spiny neurons (MSNs) of the striatum in brain slice preparations, using a whole-cell patch-clamp technique. We found that sevoflurane slightly depolarized principal neurons in the cortex and the striatum without a significant alteration in spike threshold. Furthermore, it depressed the peak, as well as the net, charge transfer of intrastriatally evoked inhibitory postsynaptic currents (eIPSCs) much more strongly than those of excitatory postsynaptic currents (EPSCs), and this inhibition was accompanied by an elevated paired-pulse ratio. The strong suppression of eIPSCs paralleled a significant suppression of the frequency, but not the amplitude, of miniature IPSCs (mIPSCs), and was associated with a transient increase in the frequency of spontaneous EPSCs. Treatment with the Ca(2+) channel blocker Cd(2+) restored the frequency of mIPSCs to the control level, indicating sevoflurane's strong presynaptic suppression of γ-aminobutyric acid release in the striatum. In contrast, in hippocampal CA1 pyramidal neurons sevoflurane produced an enhancement of the net charge transfer of IPSCs, while it suppressed EPSCs to an equivalent degree to that in striatal MSNs. These results suggest that, in contrast to its effects on other brain structures, sevoflurane shifts the balance between synaptic excitation and inhibition in the direction of excitation in the striatum, thereby causing involuntary movements during induction of anesthesia by sevoflurane.
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