Margalit Shany Nivinsky, Golomb Neta Gery, Tsur Omer, Ben Yehoshua Eve, Raz Aeyal, Slovin Hamutal
The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel.
Department of Anesthesiology, Rambam Health Care Campus, Haifa, 3109601, Israel and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Cereb Cortex. 2022 Dec 8;32(24):5512-5529. doi: 10.1093/cercor/bhac031.
Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Isoflurane is a commonly used anesthetic drug; however, its effects on cortical sensory processing, in particular around LOC, are not well understood. Using voltage-sensitive dye imaging, we measured visually evoked neuronal population response from the visual cortex in awake and anesthetized mice at 3 increasing concentrations of isoflurane, thus controlling the level of anesthesia from wakefulness to deep anesthesia. At low concentration of isoflurane, the effects on neuronal measures were minor relative to the awake condition. These effects augmented with increasing isoflurane concentration, while around LOC point, they showed abrupt and nonlinear changes. At the network level, we found that isoflurane decreased the stimulus-evoked intra-areal spatial spread of local neural activation, previously reported to be mediated by horizontal connections, and also reduced intra-areal synchronization of neuronal population. The synchronization between different visual areas decreased with higher isoflurane levels. Isoflurane reduced the population response amplitude and prolonged their latencies while higher visual areas showed increased vulnerability to isoflurane concentration. Our results uncover the changes in neural activity and synchronization at isoflurane concentrations leading to LOC and suggest reverse hierarchical shutdown of cortical areas.
麻醉药物在医学和研究中被广泛用于诱导意识丧失（LOC）。异氟烷是一种常用的麻醉药物；然而，其对皮质感觉处理的影响，特别是在LOC前后的影响，尚未得到充分理解。我们使用电压敏感染料成像技术，在清醒和麻醉的小鼠中，以3种递增浓度的异氟烷测量了视觉皮层的视觉诱发神经元群体反应，从而控制从清醒到深度麻醉的麻醉水平。在低浓度异氟烷时，相对于清醒状态，对神经元测量的影响较小。这些影响随着异氟烷浓度的增加而增强，而在LOC点附近，它们表现出突然的非线性变化。在网络层面，我们发现异氟烷减少了刺激诱发的局部神经激活在区域内的空间扩散，此前报道这种扩散由水平连接介导，并且还降低了神经元群体的区域内同步性。随着异氟烷水平升高，不同视觉区域之间的同步性降低。异氟烷降低了群体反应幅度并延长了其潜伏期，而较高的视觉区域对异氟烷浓度表现出更高的敏感性。我们的结果揭示了导致LOC的异氟烷浓度下神经活动和同步性的变化，并表明皮质区域存在反向层级关闭。
