Cortical mechanism of unconsciousness

暂时性意识丧失是动物物种中普遍存在的现象。它是在我们入睡时自然发生的，但也可以通过使用特定的药物人工诱导。尽管这种行为很普遍，但人们对从清醒到昏迷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麻醉剂对啮齿动物细胞水平上的皮质功能的影响，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将深皮质锥体神经元的躯体和顶端树突间分开，这样在浅层树突处接收的信息就不会传递到胞体。这一发现与我的实验室的中心主题-树突假说-很好地一致，该假说指出，意识知觉依赖于大脑皮质中通过L5锥体神经元整合的前馈和反馈信息流(Larkum，2013)。此外，我们最近还表明，L5顶端树突的下调活动干扰了感觉输入的检测(Takahashi等人，2016；Takahashi等人，在出版中)。综上所述，我们假设分离L5细胞的树突状和体细胞隔间会扰乱意识体验。很明显，睡眠也伴随着不同的意识状态，然而，目前尚不清楚睡眠中的无意识与麻醉的机制是否相同，甚至相似。在这里，我们提出了一系列实验，结合先进的神经生理学技术，旨在确定L5皮质锥体神经元的树突和躯体隔间在睡眠的不同阶段是否分离。

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.