Propofol-mediated impairment of CA1 long-term potentiation in mouse hippocampal slices

Propofol (2,6-diisopropylphenol) is a short-acting intravenous anesthetic. Propofol is known to impair maintenance of long-term potentiation (LTP) in synaptic responses from Schaffer collateral-commissural (SC) pathway to CA1 pyramidal cells in the hippocampus, but the threshold concentration of propofol needed to elicit this action is unknown. The actions of propofol in vivo (e.g., amnesia, sedation, hypnosis and immobility) depend on its concentration, and thus it is necessary to determine the concentration required to impair CA1 LTP in order to assess the impact of impairment in vivo. In the present study, we investigated the effects of various concentrations of propofol on synaptic plasticity, primarily by measuring LTP at SC pathway to CA1 pyramidal cell synapses in mouse hippocampal slices. Continuous application of 50 μM propofol from 20 min before tetanus stimulation suppressed potentiation of the synaptic responses by tetanus stimulation. The suppression was pronounced from 10 min post-tetanus and about 55% suppression of the potentiation was observed at 60 min after tetanus. Propofol at 5 or 20 μM did not have this effect. The presence of γ-aminobutyric acid type A (GABAA) receptors antagonist, picrotoxin, abrogated the suppression of LTP by 50 μM propofol. Propofol 50 μM did not affect long-term depression (LTD). These results suggest that the suppression of hippocampal CA1 LTP via GABAA receptors requires a much higher propofol concentration compared with that needed to induce amnesia.