Frequency-selective control of cortical and subcortical networks by central thalamus.
Frequency-selective control of cortical and subcortical networks by central thalamus.
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作者：
Liu J;Lee HJ;Weitz AJ;Fang Z;Lin P;Choy M;Fisher R;Pinskiy V;Tolpygo A;Mitra P;Schiff N;Lee JH
中央丘脑在前脑唤醒和组织行为中起着至关重要的作用。然而，将其活动与大脑状态联系起来的网络级机制仍然是个谜。在这里，我们结合了光遗传学、功能磁共振成像、电生理学和视频脑电图监测来表征负责切换大脑状态的中央丘脑驱动的全球大脑网络。对中央丘脑的 40 和 100 Hz 刺激引起前脑的广泛激活，包括额叶皮层、感觉运动皮层和纹状体，并使睡眠大鼠的大脑转变为唤醒状态。相比之下，10 Hz 刺激引起的前脑激活、感觉皮层抑制和行为停滞明显减少。为了研究频率依赖性皮质抑制的可能机制，我们在未定带中进行了记录，其中 10 Hz（但不是 40 Hz）刺激引起了纺锤样振荡。重要的是，在 10 Hz 中央丘脑刺激期间抑制偶然活动会减少诱发的皮质抑制。这些发现确定了中央丘脑唤醒调节背后的关键全脑动态。 DOI：http://dx.doi.org/10.7554/eLife.09215.001 大多数人认为每天早上醒来并晚上入睡的能力是理所当然的。然而，中央丘脑的大脑区域受损可能会导致一系列与意识相关的疾病，包括记忆问题、过度睡眠，甚至昏迷。例如，中央丘脑内的细胞死亡与创伤性脑损伤后严重残疾的患者有关。先前的研究发现，电刺激中央丘脑的神经元可以改变动物是昏昏欲睡还是清醒警觉。然而，尚不清楚中央丘脑中的一组神经元是否负责在睡眠和清醒之间切换大脑状态，或者它是如何工作的。刘、李、韦茨、方等人。现在已经使用一种称为光遗传学的技术，通过闪光来刺激大鼠中央丘脑的特定神经元。刺激与多种技术相结合来监测其他大脑区域的反应，包括显示整个大脑活动的功能磁共振成像。结果表明，快速刺激中央丘脑的神经元（每秒 40 或 100 次）会导致广泛的大脑活动，并使熟睡的老鼠醒来。相比之下，更缓慢地刺激中央丘脑的神经元（大约每秒 10 次）会抑制大脑中称为感觉皮层的部分的活动，并导致老鼠进入癫痫样的无意识状态。进一步的研究发现了一组与中央丘脑相互作用以进行这种抑制的抑制性神经元。结果表明，中央丘脑可以使大脑进入“清醒”状态，也可以促进无意识状态，具体取决于其神经元受到刺激的速度。未来的工作将寻求将这些结果转化为临床，并研究如何优化中央丘脑的刺激以减少创伤性脑损伤动物模型的认知缺陷。 DOI：http://dx.doi.org/10.7554/eLife.09215.002
Central thalamus plays a critical role in forebrain arousal and organized behavior. However, network-level mechanisms that link its activity to brain state remain enigmatic. Here, we combined optogenetics, fMRI, electrophysiology, and video-EEG monitoring to characterize the central thalamus-driven global brain networks responsible for switching brain state. 40 and 100 Hz stimulations of central thalamus caused widespread activation of forebrain, including frontal cortex, sensorimotor cortex, and striatum, and transitioned the brain to a state of arousal in asleep rats. In contrast, 10 Hz stimulation evoked significantly less activation of forebrain, inhibition of sensory cortex, and behavioral arrest. To investigate possible mechanisms underlying the frequency-dependent cortical inhibition, we performed recordings in zona incerta, where 10, but not 40, Hz stimulation evoked spindle-like oscillations. Importantly, suppressing incertal activity during 10 Hz central thalamus stimulation reduced the evoked cortical inhibition. These findings identify key brain-wide dynamics underlying central thalamus arousal regulation. DOI: http://dx.doi.org/10.7554/eLife.09215.001 The ability to wake up every morning and to fall asleep at night is something that most people take for granted. However, damage to a brain region called the central thalamus can cause a range of consciousness-related disorders, including memory problems, excessive sleeping, and even comas. For example, cell death within the central thalamus has been associated with severely disabled patients following traumatic brain injury. Previous studies have found that electrically stimulating the neurons in the central thalamus can change whether an animal is drowsy or awake and alert. However, it was not clear whether a single group of neurons in the central thalamus was responsible for switching the brain’s state between sleep and wakefulness, or how this would work. Liu, Lee, Weitz, Fang et al. have now used a technique called optogenetics to stimulate specific neurons in the central thalamus of rats, by using flashes of light. Stimulation was combined with several techniques to monitor the response of other brain regions, including fMRI imaging that shows the activity of the entire brain. The results showed that rapidly stimulating the neurons in the central thalamus – 40 or 100 times a second – led to widespread brain activity and caused sleeping rats to wake up. In contrast, stimulating the neurons of the central thalamus more slowly – around 10 times a second – suppressed the activity of part of the brain called the sensory cortex and caused rats to enter a seizure-like state of unconsciousness. Further investigation identified a group of inhibitory neurons that the central thalamus interacts with to carry out this suppression. The results suggest that the central thalamus can either power the brain to an “awake” state or promote a state of unconsciousness, depending on how rapidly its neurons are stimulated. Future work will seek to translate these results to the clinic and investigate how stimulation of the central thalamus can be optimized to reduce cognitive deficits in animal models of traumatic brain injury. DOI: http://dx.doi.org/10.7554/eLife.09215.002