Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin Madison, WI, USA ; Department of Anesthesiology, Rabin Medical Center, Petah-Tikva, Israel, Affiliated with Sackler School of Medicine, Tel Aviv University Tel Aviv, Israel.
Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin Madison, WI, USA.
Front Syst Neurosci. 2014 Oct 7;8:191. doi: 10.3389/fnsys.2014.00191. eCollection 2014.
The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.
麻醉下意识丧失（LOC）的机制尚不清楚。由于意识依赖于皮质丘脑网络的活动，因此麻醉作用于该网络对于 LOC 可能至关重要。竞争理论强调麻醉作用于自上而下的“核心”丘脑皮质（TC）与自下而上的皮质皮质（CC）和基质 TC 连接的重要性。我们使用体内大鼠听觉皮层的层记录和鼠脑切片测试了这些模型。我们使用体内感觉刺激和脑切片中的电刺激选择性地激活自下而上与自上而下的传入途径，并比较了异氟醚对通过两种途径诱发的反应的影响。体内听觉刺激和脑切片中的核心 TC 传入刺激在中层诱发潜伏期短的电流汇，与核心 TC 传入的激活一致。相比之下，体内视觉刺激和脑切片中 CC 和基质 TC 传入的刺激在浅层和深层诱发反应，与携带视觉信息到听觉皮层的自上而下传入的投射模式一致。与体内视觉刺激和 CC/matrix TC 传入引起的反应相比，体内听觉刺激和脑切片中的核心 TC 传入引起的反应受异氟醚的影响明显较小。在体内催眠剂量下，异氟醚增强了听觉反应，而视觉反应则显著降低。在切片中的可比浓度下，异氟醚抑制了核心 TC 和 CC/matrix TC 的反应，但对后者的影响远大于对核心 TC 的影响，表明在体内观察到的差异效应至少部分归因于异氟醚在听觉皮层中的局部作用。这些数据支持一种模型，即破坏自上而下的连通性有助于麻醉诱导的 LOC，并对理解意识的神经基础具有重要意义。
