Cortical mechanism of unconsciousness

暂时性意识丧失是动物物种中普遍存在的现象。当我们入睡时，它会自然发生，但也可以通过使用特定药物人为诱导。尽管这种行为很普遍，但人们对从清醒到无意识转变的确切生理机制知之甚少。我实验室最近的工作通过研究几种不同的麻醉剂对啮齿动物细胞水平上皮质功能的影响，为这个谜团提供了新的见解（Suzuki和Larkum，2020）。我们发现，这些药物的一个共同作用是解耦深皮质锥体神经元的体细胞和顶端树突隔室，因此在表面树突接收的输入不会被传递到索马。这一发现与我实验室的中心主题非常一致，即树枝状假说，该假说指出，意识感知依赖于通过L5锥体神经元在皮层中整合前馈和反馈信息流（Larkum，2013）。此外，我们最近还表明，下调L5顶端树突的活性会干扰感觉输入的检测（Takahashi et al，2016; Takahashi et al，in press）。综上所述，我们假设L5细胞的树突和体细胞区室的分离破坏了意识体验。很明显，睡眠也需要各种意识状态，但不知道睡眠和麻醉中的无意识机制是否相同或相似。 在这里，我们提出了一系列的实验，使用尖端的神经生理学技术相结合，旨在确定L5皮层锥体神经元的树突和体细胞隔室是否在睡眠的不同阶段解耦。

Temporary loss of consciousness is a ubiquitous phenomenon across animal species. It occurs organically when we fall asleep but can also be induced artificially through use of specific drugs. Despite the prevalence of this behaviour, the precise physiological mechanisms underlying the transition from awake to unconsciousness are poorly understood. Recent work from my lab has offered novel insight into this mystery by studying the effects of several different anaesthetics on cortical function at a cellular level in rodents (Suzuki and Larkum, 2020). We discovered that a common effect of these drugs was to decouple the somatic and apical dendritic compartments of deep cortical pyramidal neurons, so that inputs received at superficial dendrites would not be transmitted to the soma. This finding coheres nicely with the central theme of my lab, namely the Dendrite Hypothesis, which states that conscious perception is dependent on the integration of feedforward and feedback information streams in the cortex via L5 pyramidal neurons (Larkum, 2013). Moreover, we have also recently shown that downregulating activity in L5 apical dendrites interferes with the detection of a sensory input (Takahashi et al, 2016; Takahashi et al, in press). Taken together, we hypothesize that decoupling the dendritic and somatic compartments of L5 cells disrupts conscious experience. It is clear that sleep also entails various states of consciousness, however it is not known whether the mechanisms for unconsciousness in sleep and anaesthesia are the same or even similar. Here, we propose a series of experiments, using a combination of cutting edge neurophysiology techniques, designed to determine whether the dendritic and somatic compartments of L5 cortical pyramidal neurons are decoupled during different stages of sleep.