Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus

Hu，Jiang Jian1,2; Liu，Yuexin1,2; Yao，Hongyu1,2; Cao，Boxu1,2; Liao，Huabao1,2; Yang，Ruodi2; Chen，Peng1,2; Song，Xue Jun1,2

2023

10.1038/s41593-023-01290-y

Nature Neuroscience   Impact Factor & Quartile

1097-6256

1546-1726

The emergence of consciousness from anesthesia, once assumed to be a passive process, is now considered as an active and controllable process. In the present study, we show in mice that, when the brain is forced into a minimum responsive state by diverse anesthetics, a rapid downregulation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) serves as a common mechanism by which the brain regains consciousness. Ubiquitin-proteasomal degradation is responsible for KCC2 downregulation, which is driven by ubiquitin ligase Fbxl4. Phosphorylation of KCC2 at Thr1007 promotes interaction between KCC2 and Fbxl4. KCC2 downregulation leads to γ-aminobutyric acid type A receptor-mediated disinhibition, enabling accelerated recovery of VPM neuron excitability and emergence of consciousness from anesthetic inhibition. This pathway to recovery is an active process and occurs independent of anesthetic choice. The present study demonstrates that ubiquitin degradation of KCC2 in the VPM is an important intermediate step en route to emergence of consciousness from anesthesia.

English

NI Journal Papers

First

NEUROSCIENCE & BEHAVIOR

2-s2.0-85150894332

Scopus

1.Department of Medical Neuroscience,School of Medicine,Southern University of Science and Technology,Shenzhen,China
2.SUSTech Center for Pain Medicine,Southern University of Science and Technology,Shenzhen,China

Hu，Jiang Jian,Liu，Yuexin,Yao，Hongyu,et al. Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus[J]. Nature Neuroscience,2023.

Hu，Jiang Jian.,Liu，Yuexin.,Yao，Hongyu.,Cao，Boxu.,Liao，Huabao.,...&Song，Xue Jun.(2023).Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus.Nature Neuroscience.

Hu，Jiang Jian,et al."Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus".Nature Neuroscience (2023).