Physiology Graduate Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Br J Anaesth. 2019 Oct;123(4):488-496. doi: 10.1016/j.bja.2019.06.018. Epub 2019 Aug 2.
General anaesthetics affect loss of consciousness by disrupting information-passing and integration within thalamo-cortical (TC) networks. Feedback cortical connections that carry internally generated signals such as expectation and attention appear more sensitive to anaesthesia than feedforward signals. However, direct evidence for this effect in non-primary cortex is lacking. In addition, direct comparisons between TC core and matrix, and between cortico-cortical (CC) feedforward and feedback responses have not been reported.
We investigated the disruption of synaptic responses by isoflurane of four distinct afferent pathways to non-primary neocortex. We independently activated TC core and matrix and reciprocal CC (feedforward and feedback) pathways using optogenetic techniques, and compared the relative sensitivity of synaptic responses to isoflurane.
Under control conditions, activation of axon terminals of all pathways evoked postsynaptic currents (recorded extracellularly) and postsynaptic potentials in pyramidal neurones. CC feedback responses were substantially more sensitive to isoflurane (0 to 0.53 mM) compared with TC core, TC matrix, or CC feedforward pathways.
Differential sensitivity of CC feedback synaptic responses to isoflurane in a clinically relevant range suggests a role for disruption of these afferents in the hypnotic effects of anaesthetic agents.
全身麻醉通过扰乱丘脑-皮质（TC）网络内的信息传递和整合来影响意识丧失。携带内部生成信号（如期望和注意）的反馈皮质连接似乎比前馈信号对麻醉更敏感。然而，非主要皮质中缺乏这种效应的直接证据。此外，TC 核心和基质之间以及皮质-皮质（CC）前馈和反馈反应之间的直接比较尚未报道。
我们使用光遗传学技术研究了异氟醚对非主要新皮质中四种不同传入途径的突触反应的干扰。我们分别激活 TC 核心和基质以及互感 CC（前馈和反馈）途径，并比较了突触反应对异氟醚的相对敏感性。
在对照条件下，所有途径的轴突末梢的激活都在锥体细胞中诱发了突触后电流（在体外记录）和突触后电位。与 TC 核心、TC 基质或 CC 前馈途径相比，CC 反馈反应对异氟醚（0 至 0.53mM）的敏感性要高得多。
CC 反馈突触反应对异氟醚在临床相关范围内的敏感性差异表明，这些传入纤维的破坏在麻醉剂的催眠作用中起作用。
