Cortical mechanism of unconsciousness

• Applicant: Professor Matthew Larkum
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 455520918

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.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Cooperation Partner: Julie Seibt, Ph.D.