Attenuation of High-Frequency (50-200 Hz) Thalamocortical EEG Rhythms by Propofol in Rats Is More Pronounced for the Thalamus than for the Cortex

Abstract

BackgroundThalamocortical EEG rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. To test the hypothesis that general anesthetics attenuate these rhythms, we characterized the concentration-effect relationship of propofol on the spectral power of these rhythms. In view of the ongoing debate about cortex versus thalamus as the primary site of anesthetic action for unconsciousness, we also compared the relative sensitivity of cortex and thalamus to this effect propofol.MethodsAdult male Long-Evans rats were chronically implanted with electrodes in somatosensory (barrel) cortex and ventroposteromedial thalamus. Propofol was delivered by a computer-controlled infusion using real-time pharmacokinetic modeling to obtain the desired plasma concentration. Spectral power was assessed during baseline, at four stable propofol plasma-concentrations (0, 3,6,9,12 μg/ml) and during recovery over four frequency ranges (30-50, 51-75, 76-125, 126-200 Hz). Unconsciousness was defined as complete loss of righting reflex. Multiple regression was used to model the change of power (after logarithmic transformation) as a function of propofol concentration and recording site.ResultsUnconsciousness occurred at the 9 μg/ml concentration in all animals. Propofol caused a robust linear concentration-dependent attenuation of cortical power in the 76-200 Hz range and of thalamic power in the 51-200 Hz range. In all instances the concentration-effect slope for the thalamus was markedly steeper than for the cortex. Furthermore the lowest concentration causing unconsciousness significantly reduced cortical power in the 126-200 Hz range and thalamic power in the 51-200 Hz range.ConclusionsPropofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 51-200 Hz range and this effect is far more pronounced for the thalamus, where the attenuation provides a robust correlate of the hypnotic action of propofol.

A comparison of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation on visual and motor cortical oscillations, using magnetoencephalography

“…This effect on thalamic oscillations is less prominent with dexmedetomidine as compared to propofol, at frequencies > 50 Hz. While dexmedetomidine affects thalamic and cortical oscillations to a similar extent, propofol has a much greater effect on thalamic oscillations than cortical oscillations 14 .…”

Anesthetic Suppression of Thalamic High-Frequency Oscillations: Evidence that the Thalamus Is More Than Just a Gateway to Consciousness?

“…Plourde et al confirm that like propofol, 22 isoflurane attenuates thalamic gamma frequency oscillations (30 – 200 Hz) in a concentration-dependent manner. 5 They also demonstrate that isoflurane attenuates these gamma frequency oscillations in the cortex to a greater extent than does propofol.…”

“…The findings of Plourde et al 5,22 bring us one step closer in our epic quest to understand how anesthetics affect the brain. A full answer to this question 1 will require multiple levels of analysis, from an understanding of how the molecular effects of anesthetics give rise to alterations in cellular and synaptic function, which then change circuit and brain region level activity patterns to ultimately produce the cognitive and behavioral picture that we intuitively recognize as general anesthesia.…”

“…5 They also demonstrate that isoflurane attenuates these gamma frequency oscillations in the cortex to a greater extent than does propofol. 22 The authors used concentrations of isoflurane and propofol that were equipotent at producing loss of the righting reflex, but they note that their results may have differed if using alternative behavioral endpoints that require higher anesthetic doses (e.g., suppressing reaction to noxious stimulation). Perhaps most importantly, for both propofol and isoflurane, the suppression of high gamma frequency oscillations was more pronounced in the thalamus than the cerebral cortex.…”

“…The thalamic field potential recording data presented by Plourde and colleagues 5,22 force us to reconsider this view. Local field potential recordings mainly represent postsynaptic dendritic depolarizations rather than axonal action potentials.…”