Cortical inhibition during burst suppression induced with isoflurane anesthesia

Area of Science:

• Neuroscience
• Anesthesiology
• Neurophysiology

Background:

• Isoflurane anesthesia induces burst suppression (BS), a state characterized by electroencephalographic patterns and cortical hyperexcitability.
• The underlying mechanisms of BS-associated cortical hyperexcitability, particularly changes in neuronal inhibition, require further investigation.

Purpose of the Study:

• To investigate the hypothesis that diminished cortical inhibition contributes to isoflurane-induced burst suppression (BS).
• To elucidate the specific mechanisms responsible for altered neuronal inhibition during BS.

Main Methods:

• In vivo intracellular recordings of cortical neurons in response to thalamic nucleus stimulation.
• Assessment of excitatory postsynaptic potentials (EPSPs) and inhibitory potentials.
• Measurement of neuronal input resistance.
• Evaluation of GABA receptor availability via iontophoresis.
• Analysis of extracellular chloride concentration.
• Pharmacological manipulation using dihydrokainate to block glial glutamate transporters.

Main Results:

• During BS, EPSPs were reduced by 44%, and inhibitory potentials were completely suppressed.
• The typical decrease in neuronal input resistance during inhibition was abolished under BS conditions.
• Removal of inhibition revealed previously masked excitatory components.
• GABA receptors remained available, and extracellular chloride increased, suggesting preserved receptor function.
• Blockage of glial glutamate transporters with dihydrokainate reinstated inhibitory responses.

Conclusions:

• Isoflurane-induced BS is characterized by a profound lack of cortical inhibition.
• This inhibition deficit is likely caused by increased glial glutamate uptake, stimulated by isoflurane, leading to reduced activation of cortical interneurons.
• The findings suggest that suppressed inhibition, rather than direct excitation, favors cortical hyperexcitability during BS.