Use of RHO GTPase by L1 GABAergic neurons in frontal cortex and L6 glutamatergic neurons in prefrontal cortex differentiates states of unconsciousness

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Abstract

Unconsciousness can be induced by sleep and general anaesthesia alike; however, the extent to which these states differ is not well understood. In this study, we aimed to determine the similarities and differences between the unconscious states caused by sleep and those caused by anaesthesia, as well as investigate gene expression profiles by applying tensor decomposition-based unsupervised feature extraction to the two gene expression profiles. One of the two expression profiles was obtained from mice treated with sevoflurane, a type of inhaled anaesthesia, whereas the other two expression profiles were obtained from sleeping and awake mice. We selected two sets of genes (507 and 1048 genes) that were distinctly expressed between sleep- or anaesthesia-induced unconsciousness and the awake state. Both sets of genes include various distinct genes which are common to the state of unconsciousness during sleep and anaesthesia. The former was enriched in GABAergic synapses and the first layer of the frontal cortex, whereas the latter was enriched in glutamatergic synapses and the sixth layer of the prefrontal cortex. Additionally, both sets of genes were enriched in the RHO GTPase pathway. Based on these results, we hypothesised that L1 GABAergic neurons in the frontal cortex and L6 glutamatergic neurons in the prefrontal cortex use RHO GTPase to differentiate between the states of unconsciousness induced by general anaesthesia and sleep.
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Abstract Unconsciousness can be induced by sleep and general anaesthesia alike; however, the extent to which these states differ is not well understood. In this study, we aimed to determine the similarities and differences between the unconscious states caused by sleep and those caused by anaesthesia, as well as investigate gene expression profiles by applying tensor decomposition-based unsupervised feature extraction to the two gene expression profiles. One of the two expression profiles was obtained from mice treated with sevoflurane, a type of inhaled anaesthesia, whereas the other two expression profiles were obtained from sleeping and awake mice. We selected two sets of genes (507 and 1048 genes) that were distinctly expressed between sleep- or anaesthesia-induced unconsciousness and the awake state. Both sets of genes include various distinct genes which are common to the state of unconsciousness during sleep and anaesthesia. The former was enriched in GABAergic synapses and the first layer of the frontal cortex, whereas the latter was enriched in glutamatergic synapses and the sixth layer of the prefrontal cortex. Additionally, both sets of genes were enriched in the RHO GTPase pathway. Based on these results, we hypothesised that L1 GABAergic neurons in the frontal cortex and L6 glutamatergic neurons in the prefrontal cortex use RHO GTPase to differentiate between the states of unconsciousness induced by general anaesthesia and sleep. Competing Interest Statement The authors have declared no competing interest. Footnotes Revision due to the reviewers' comment

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