Cortical Inhibition during Burst Suppression Induced with Isoflurane Anesthesia

Abstract

Isoflurane is a widely used anesthetic which safely and reversibly induces deep coma and associated burst suppression (BS) electroencephalographic patterns. Here we investigate possible underlying causes for the state of cortical hyperexcitability which was recently shown to be one of the characteristics of BS. Our hypothesis was that cortical inhibition is diminished during isoflurane-induced BS. Experiments were performed in vivo using intracellular recordings of cortical neurons to assess their responsiveness to stimulations of connected thalamic nuclei. We demonstrate that during BS EPSPs were diminished by 44%, whereas inhibitory potentials were completely suppressed. This finding was supported by additional results indicating that a decrease in neuronal input resistance normally found during inhibitory responses under low isoflurane conditions was abolished in the BS condition. Moreover, removal of inhibition occasionally revealed excitatory components which were absent during recordings before the induction of BS. We also show that the absence of inhibition during BS is not caused by a blockage of GABA receptors, since iontophoretically applied GABA shows receptor availability. Moreover, the concentration of extracellular chloride was increased during BS, as would be expected after reduced flow of chloride through GABA A receptors. Also inhibitory responses were reinstated by selective blockage of glial glutamate transporters with dihydrokainate. These results suggest that the lack of inhibition during BS is caused by reduced excitation, probably resulting from increased glial uptake of glutamate stimulated by isoflurane, which creates a diminished activation of cortical interneurons. Thus cortical hyperexcitability during BS is favored by suppressed inhibition.

Spike-Train Communities: Finding Groups of Similar Spike Trains

“…These maximum ⌬Q were found for Gaussian widths between 0.116 and 0.289 s (corresponding to bin sizes between 0.4 and 1 s) in each window (Fig. 6 B), consistent with the detected correlated activity following the Ͻ1 Hz slow-wave oscillations under isoflurane (Ferron et al, 2009). The number of groups giving maximum ⌬Q was predominantly two, and occasionally three or four (Fig.…”

“…The less-dominated group also had occasional brief periods of simultaneous spiking, and a sustained period of spiking lasting Ͼ10 s. The population activities of the two groups' were antiphase at very low frequencies (Ͻ0.4 Hz), but in phase at the slightly higher frequencies (0.5-1 Hz) that normally comprise the peaks in cortical EEG/LFP spectra (Ferron et al, 2009). Thus, the detected groups at this timescale correspond to neurons with an anti-phase, very slow oscillation, upon which is superimposed the widely reported in-phase ϳ1 Hz slow-oscillation.…”

“…I used the algorithm to search for patterns across all 50 spike trains in a sliding window of 50 s, applied every 10 s-the sliding window allowed me to look at nonstationary structure over such a long, continuous recording. As these recordings were under isoflurane anesthetic, I decided to look for large timescale structure of the spontaneous activity, potentially locked to slow (Ͻ1 Hz), cortex-wide oscillations (Ferron et al, 2009). Supplemental Figure 4 (available at www.jneurosci.org as supplemental material) confirms that the power spectra of spike trains in both V1 and V2 were dominated by Ͻ1 Hz components throughout the recordings used here.…”

Implication of Kir4.1 Channel in Excess Potassium Clearance: AnIn VivoStudy on Anesthetized Glial-Conditional Kir4.1 Knock-Out Mice

“…Therefore, the low input resistance obtained in this study might reflect only the somatic domain, with possible contributions from the currents through gap junctions. Indeed, the closure of gap junctions with high concentrations of isoflurane has produced higher input resistance in a subpopulation of cat glial cells (Ferron et al, 2009).…”

A neurophysiological–metabolic model for burst suppression

“…In particular, the early work of Steriade et al (10) helped establish the neural correlates of burst suppression, including the differential participation of cortical and subcortical cell types. More recent studies (11,12) have suggested that burst suppression is associated with enhanced excitability in cortical networks. These studies implicate extracellular calcium as a correlate for the switches between burst and suppression.…”