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

• Published in: The European journal of neuroscience Vol. 35; no. 9; pp. 1396 - 1405
• Main Authors: Oose, Yoshiyuki, Miura, Masami, Inoue, Ritsuko, Andou, Nozomi, Aosaki, Toshihiko, Nishimura, Kinya
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2012
• Subjects: Alveoli; Anesthesia; Anesthetics - pharmacology; Animals; Animals, Newborn; brain slice; Brain slice preparation; CA1 Region, Hippocampal - cytology; Cadmium Chloride - pharmacology; Calcium; Calcium Channel Blockers - pharmacology; Cerebral Cortex - cytology; Corpus Striatum - cytology; Cortex; Dose-Response Relationship, Drug; excitatory postsynaptic currents; Excitatory postsynaptic potentials; Excitatory Postsynaptic Potentials - drug effects; gamma -Aminobutyric acid; Hippocampus; In Vitro Techniques; inhibitory postsynaptic currents; Inhibitory postsynaptic potentials; Inhibitory Postsynaptic Potentials - drug effects; Methyl Ethers - pharmacology; Mice; Mice, Inbred BALB C; Neostriatum; Nervous system; Neurons - drug effects; patch-clamp; Patch-Clamp Techniques; Pyramidal cells; Reaction Time - drug effects; Sevoflurane; spiny neurons; Synaptic transmission; Time Factors
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2012.08065.x

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 Ca2+ channel blocker Cd2+ 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. 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 (2 MAC) on the electrophysiological activities of the medium spiny neurons (MSNs) of the striatum in brain slice preparations, using a whole‐cell patch‐clamp technique.