Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex.
Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex.
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DOI：
10.3389/fnsys.2014.00191
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发表时间：
2014
影响因子：
3
通讯作者：
Banks MI
中科院分区：
文献类型：
--
作者：
Raz A;Grady SM;Krause BM;Uhlrich DJ;Manning KA;Banks MI
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，因此该网络上的麻醉作用可能对 LOC 至关重要。相互竞争的理论强调麻醉作用对自下而上的“核心”丘脑皮质 (TC) 与自上而下的皮质皮质 (CC) 和矩阵 TC 连接的重要性。我们使用大鼠体内听觉皮层的层流录音和小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和自上而下的传入通路，并比较异氟烷对通过这两种通路引起的反应的影响。体内听觉刺激和脑切片中的核心 TC 传入刺激引起中层的短潜伏电流吸收，这与核心 TC 传入的激活一致。相比之下，体内视觉刺激以及脑切片中 CC 和基质 TC 传入神经的刺激主要在浅层和深层引起反应，这与将视觉信息传递到听觉皮层的自上而下传入神经的投射模式一致。与体内视觉刺激和切片中 CC/矩阵 TC 传入触发的反应相比，异氟烷对体内听觉刺激和脑切片中核心 TC 传入的反应明显较小。在体内的催眠剂量下，异氟烷增强了听觉反应，而视觉反应则急剧降低。在切片中的相当浓度下，异氟醚抑制核心 TC 和 CC/基质 TC 反应，但对后者反应的影响远远大于对核心 TC 反应，表明体内观察到的差异效应的至少部分是由于异氟醚在听觉皮层中的局部作用。这些数据支持一个模型，其中自上而下连接的破坏有助于麻醉引起的 LOC，并且对理解意识的神经基础具有影响。
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.