Anesthetic-induced Burst Suppression EEG Activity Requires Glutamate-mediated Excitatory Synaptic Transmission

Many anesthetics evoke electroencephalogram (EEG) burst sup-pression activity in humans and animals during anesthesia, and the mechanisms underlying this activity remain unclear. The present study used a rat neocortical brain slice EEG preparation to investigate excitatory synapticmechanisms underlying anesthetic-induced burst suppression activity. Excitatory synaptic mechanisms associated with burst suppression activity were probed using glutamate re-ceptor antagonists (CNQX and APV), GABA receptor antagonists, and simultaneous whole cell patch clamp and microelectrode EEG recor-dings. Clinically relevant concentrations of thiopental (50--70 mM), propofol (5--10 mM) or isoflurane (0.7--2.1 vol%, 0.5--1.5 rat minimum aveolar concentration (MAC), 200--700 mM) evoked delta slow wave activity and burst suppression EEG patterns similar to in vivo responses. These effects on EEG signals were blocked by glutamate receptor antagonists CNQX (8.6 mM) or APV (50 mM). Depolarizing intracellular bursts (amplitude5 34.76 4.5 mV; half width5 1326 60 ms) always accompanied EEG bursts, and hyperpolarization increased intracellular burst amplitudes. Barrages of glutamate-mediated excitatory events initiated EEGbursting activity. Glutamate-mediated excitatory postsynaptic currents were significantly de-pressed by higher anesthetic concentrations that depressed burst suppression EEG activity. A GABAA agonist produced a similar EEG effect to the anesthetics. It appears that anesthetic effects at both glutamate andGABA synapses contribute to EEGpatterns seen during anesthesia