Facilitatory effects of subanesthetic sevoflurane on excitatory synaptic transmission and synaptic plasticity in the mouse hippocampal CA1 area.

摘要

Behavioral investigations have shown that general anesthetics at low concentration have enhancing effects on learning and memory in some animal models. In the present experiments, in order to elucidate the cellular mechanisms underlying such memory enhancement, the effects of anesthetics at low doses on synaptic plasticity in the hippocampus were investigated. Tight-seal whole-cell recordings were made from CA1 pyramidal cells in hippocampal slices prepared from adult male mice, and the effects of subanesthetic concentrations of the volatile anesthetic sevoflurane on the glutamatergic excitatory postsynaptic currents (EPSCs) were investigated. In addition, extracellular recordings of field excitatory postsynaptic potential (fEPSP) and population spike (PS) were made, and the effects of subanesthetic sevoflurane on long-term potentiation (LTP) of the fEPSP slope and on LTP of PS amplitude were analyzed. Sevoflurane at anesthetic concentration inhibited the amplitude of EPSCs with an increase in the paired-pulse facilitation (PPF) ratio. In contrast, subanesthetic sevoflurane increased the amplitude of EPSCs without any appreciable changes in the PPF ratio. Subanesthetic sevoflurane also showed facilitatory influences on LTP of PS amplitude but not on LTP of the fEPSP slope. These observations suggest that sevoflurane at anesthetic concentration presynaptically inhibits excitatory synaptic transmission and at subanesthetic concentration postsynaptically enhances excitatory synaptic transmission in the hippocampal CA1 region. Further, subanesthetic sevoflurane seems to exert facilitatory effects on the EPSP-to-spike coupling process in the postsynaptic neurons. These results might provide clues as to the cellular mechanism of light level of sevoflurane anesthesia.