Anaesthesia Department, Waikato District Health Board, Hamilton, New Zealand.
Brain Res. 2022 Oct 1;1792:148018. doi: 10.1016/j.brainres.2022.148018. Epub 2022 Jul 16.
Propofol is well known to cause amnesia independent of its sedative effect. Memory consolidation processes in the hippocampus have been proposed as a target - however the neural substrates for propofol's amnesic actions remain understudied and poorly described. In particular, the potential role of the cerebral cortex has not been investigated. As an in vitro experimental model of cortical memory consolidation, potentiated cerebral cortex evoked responses were generated in mouse neocortical slices using high frequency (20 Hz) stimulation to layer IV cortical grey matter or subcortical white matter. In separate experiments, slices were pretreated with propofol at two concentrations, 2 µg/mL and 4 µg/mL, to determine the effect of clinically relevant propofol levels on the potentiation response. Only grey matter stimulation induced a significant and lasting increase in cortical evoked potential amplitude in the drug-free condition. Propofol at 2 µg/mL completely inhibited cortical evoked response potentiation, while the 4 µg/mL concentration caused a small but significant depressant effect consequent to the high frequency stimulation. These findings support the hypothesis that propofol disrupts memory consolidation and actively facilitates memory decay in the cerebral cortex. The results further highlight the importance of the cerebral cortex in the early phase of long term memory consolidation.
异丙酚众所周知可在其镇静作用之外引起遗忘。海马中的记忆巩固过程被认为是一个靶点-然而，异丙酚致遗忘作用的神经基础仍研究不足且描述不佳。特别是，大脑皮层的潜在作用尚未得到研究。作为皮质记忆巩固的体外实验模型，使用高频（20 Hz）刺激第四层皮质灰质或皮质下白质，在小鼠新皮层切片中产生增强的皮质诱发电响应。在单独的实验中，用两种浓度（2μg/ml 和 4μg/ml）的异丙酚预处理切片，以确定临床相关的异丙酚水平对增强反应的影响。只有灰质刺激在无药物条件下诱导皮质诱发电位幅度的显著和持久增加。2μg/ml 的异丙酚完全抑制皮质诱发电位增强，而 4μg/ml 的浓度由于高频刺激导致轻微但显著的抑制作用。这些发现支持异丙酚破坏皮质记忆巩固并主动促进皮质记忆消退的假说。这些结果进一步强调了大脑皮层在长时记忆巩固的早期阶段的重要性。
