Thalamic reticular nucleus induces fast and local modulation of arousal state.
Thalamic reticular nucleus induces fast and local modulation of arousal state.
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DOI：
10.7554/elife.08760
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发表时间：
2015-10-13
期刊：
影响因子：
7.7
通讯作者：
Brown EN
中科院分区：
文献类型：
--
作者：
Lewis LD;Voigts J;Flores FJ;Schmitt LI;Wilson MA;Halassa MM;Brown EN
在低唤醒状态下，如困倦和睡眠，皮层神经元表现出与神经元沉默期相关的节律性慢波活动。慢波是局部调节的，局部慢波动力学对记忆、认知和行为很重要。虽然控制整体睡眠状态的几个脑干结构现在已经得到了很好的表征，但尚未确定皮质慢波的快速和局部调制的机制。在这里，使用光遗传学和整个皮层电生理学，我们表明，局部紧张性激活丘脑网状核（TRN）迅速诱导慢波活动的空间限制区域的皮层。这些慢波类似于睡眠中看到的慢波，因为皮层单位经历了与慢波锁相的沉默期。此外，动物表现出与TRN刺激期间唤醒状态降低一致的行为变化。我们的结论是，TRN可以诱导快速调制的局部皮质状态。DOI：http://dx.doi.org/10.7554/eLife.08760.001我们通常认为睡眠是一种全局状态：整个大脑要么睡着，要么醒着。然而，最近的证据表明，当大脑的其他部分保持清醒时，大脑的较小区域可以显示出类似睡眠的活动。目前尚不清楚这些类似睡眠的大脑活动模式为何或如何出现，以及它们是否与即将入睡时发生的昏昏欲睡行为有关。刘易斯，Voigts等人使用一种称为光遗传学的技术研究了这一过程在小鼠中的作用。这项技术使基因工程小鼠成为可能，使大脑特定区域的活动可以通过光来打开或关闭。刘易斯、沃伊茨等人用光刺激大脑的不同区域，并使用能够检测单个神经元活动的微小电极跟踪由此产生的大脑活动。实验表明，刺激大脑深层结构丘脑网状核的一部分，只会导致大脑的一小部分从清醒状态转变为产生类似睡眠的脑电波模式。当一个更大的区域受到刺激时，整个大脑都会进入这种类似睡眠的模式。刺激丘脑网状核也会导致动物昏昏欲睡，它们更容易入睡，这表明大脑小部分的睡眠样活动可能有助于困倦。刘易斯、福伊茨等人“的发现确定了一个可以影响动物是醒着还是睡着的大脑开关。重要的是，他们表明睡眠可以在小的大脑区域中独立控制，丘脑网状核包含一个“地图”，允许它在一个区域或整个大脑中诱导睡眠。记忆在睡眠中得到加强，因此下一个挑战是研究丘脑网状核是否影响记忆的形成。研究结果还表明，对这一大脑区域的进一步研究可能有助于理解睡眠和清醒状态是如何由特定的神经元控制的。DOI：http://dx.doi.org/10.7554/eLife.08760.002网站
During low arousal states such as drowsiness and sleep, cortical neurons exhibit rhythmic slow wave activity associated with periods of neuronal silence. Slow waves are locally regulated, and local slow wave dynamics are important for memory, cognition, and behaviour. While several brainstem structures for controlling global sleep states have now been well characterized, a mechanism underlying fast and local modulation of cortical slow waves has not been identified. Here, using optogenetics and whole cortex electrophysiology, we show that local tonic activation of thalamic reticular nucleus (TRN) rapidly induces slow wave activity in a spatially restricted region of cortex. These slow waves resemble those seen in sleep, as cortical units undergo periods of silence phase-locked to the slow wave. Furthermore, animals exhibit behavioural changes consistent with a decrease in arousal state during TRN stimulation. We conclude that TRN can induce rapid modulation of local cortical state. DOI: http://dx.doi.org/10.7554/eLife.08760.001 We usually think of sleep as a global state: that the entire brain is either asleep or awake. However, recent evidence has suggested that smaller regions of the brain can show sleep-like activity while the rest of the brain remains awake. It is not clear why or how these sleep-like patterns of brain activity appear, and whether they are related to the drowsy behaviour that occurs when one is about to fall asleep. Lewis, Voigts et al. investigated how this process works in mice using a technique called optogenetics. This technique makes it possible to genetically engineer mice so that the activity of particular areas of the brain can be switched on or off by light. Lewis, Voigts et al. used light to stimulate different regions of the brain and tracked the resulting brain activity using tiny electrodes that are capable of detecting the activity of individual neurons. The experiments show that stimulating one part of a deep brain structure called the thalamic reticular nucleus causes just one small part of the brain to switch from being awake to producing sleep-like brain wave patterns. When a larger area is stimulated, the whole brain switches into this sleep-like pattern. Stimulation of the thalamic reticular nucleus also caused the animals to become drowsy and they were more likely to fall asleep, which suggests that sleep-like activity in small parts of the brain may contribute to drowsiness. Lewis, Voigts et al.’s findings identify a brain switch that can influence whether an animal is awake or asleep. Importantly, they show that sleep can be independently controlled in small brain regions, and that the thalamic reticular nucleus contains a ‘map’ that allows it to induce sleep in just one region, or across the whole brain. Memories are strengthened during sleep, so the next challenge is to study whether the thalamic reticular nucleus influences memory formation. The findings also suggest that further study of this brain region may be useful for understanding how the sleep and awake states are controlled by particular neurons. DOI: http://dx.doi.org/10.7554/eLife.08760.002