Fig. 1.

Propofol reduction of CMRO₂ is associated with impaired synaptic transmission in hippocampal slices. a Left, picture of hippocampal slice and sketch of typical electrodes positioning during simultaneous field potential and pO₂ recordings in the stratum pyramidale of area CA3. Middle: representation of brain slice under interface conditions. The tissue is provided with carbogen from surface and bottom and pO₂ decreases with the distance to the source of oxygen (i.e. distance to the slice bottom and surface, fading blue) providing typical depth profiles (see right, numbers in trace—distance to slice surface in µm). The oxygen gradient depends on oxygen supply, solubility (constant under experimental conditions) and cellular respiration. Simultaneously to the pO₂-measurements, changes in synaptic transmission were assessed. For this purpose, the Schaffer collaterals were electrically stimulated in the stratum radiatum of area CA1 (in the slice-picture, black dots) while population spikes were obtained with a glass microelectrode from CA3 in the vicinity of the oxygen probe. b Examples traces of 20 µm O₂-steps measured before (control (CTL), gray traces) and during treatment with 10 µM and 100 µM Propofol (red traces, left and right respectively). Using a reaction–diffusion model, CMRO₂ was calculated (gray and red curves for control and propofol, respectively). While the application of 10 µM Propofol did not altered respiration, 100 µM Propofol significantly decreased CMRO₂ (left and right quantitative analysis plots, respectively). c Changes in orthodromic, antidromic PS and PPR after treatment with 100 µM propofol (traces: gray control-condition and red Propofol-condition). Left: example PS of area CA3 consisting of an antidromic and orthodromic PS after electrical stimulation. Middle: overlay of PP during control (CTL: gray trace) and after treatment with 100 µM propofol (red dotted trace). As plotted on the right: the orthodromic PS and PPR significantly decreased indicating reduction in synaptic transmission and probability of presynaptic transmitter release. d Plots of computed relative changes in ATP and CMRO₂ during treatment with 100 µM Propofol. Left: ATP consumption decreases by ~ 25%. Middle: cytosolic ATP levels increased from 3.08 mM to 3.16 mM, while oxygen consumption rate decreased to ~ 82% (left). All plots display Mean + SEM, significance was tested using paired t tests, n.s. non significant, * < 0.05, **0.01 and ***0.001