NE contribution to rebooting unconsciousness caused by midazolam
- Department of Anesthesiology, Zhejiang University School of Medicine, China
- Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, China
- Department of Anesthesiology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, China
- Medical College of Jining Medical University, China
- Westlake Laboratory of Life Sciences and Biomedicine, China
Figures
Figure 1
The noradrenergic system is involved in recovery from midazolam administration.
(A) Number of LORR and no LORR induced by different doses of midazolam in C57BL/6J mice. (B) Rate of LORR (%) in C57BL/6J mice at different doses of midazolam. (C) Protocol for investigating changes …
Figure 2
LCNE neuronal activity is significantly reduced after midazolam administration and selective ablation of LCNE neurons hinders recovery from midazolam.
(A) A schematic of the fiber optic recording of calcium signal in the LC. (B) A schematic of the calcium signaling recording device. (C) A representative photomicrograph showing the microinjection …
Figure 3
Optogenetic or chemogenetic activation of LCNE neurons promotes recovery from midazolam.
(A) Protocol for the effect of PS of LCNE neurons with different light parameters on the recovery time of midazolam. (B) A schematic of the optogenetic instrument. (C) A representative …
Figure 4
LC-VLPO NEergic neural circuit was involved in the recovery from midazolam.
(A) Protocol for optogenetic or chemogenetic activation of LCNE neurons and recording of calcium signaling changes in VLPO. (B) A schematic of the location of optogenetic or chemogenetic virus …
Figure 5
Activation of LC-VLPO NEergic neural circuit promotes recovery from midazolam.
(A) Protocol for intra-LC/VLPO microinjection of the virus and optogenetic activation of VLPO. (B, C) Schematic of LC-VLPO long-range optogenetic activation and the location of optogenetic virus …
Figure 6
ICV injection or intra-VLPO microinjection of α1-R antagonist reverses the pro-recovery effect of optogenetic or chemogenetic activation of LCNE neurons.
(A) A schematic of ICV injection of different noradrenergic receptor agonists and antagonists. (B) A representative photomicrograph showing the tracks of cannulas implanted into the lateral …
Figure 7
Effect of ICV injection of α1-R antagonist and activation of LCNE neurons on EEG activity.
(A, D) Schematic diagram of EEG recording method. (B) EEG and spectrum of mice in vehicle + no PS, vehicle + PS, prazosin + no PS, and prazosin + PS at the Before LORR, LORR-RORR, and After RORR …
Figure 8
GABAA-R is an important mechanical binding site for midazolam in the LC.
(A) Protocol for the fiber optic recording of calcium signals in the LC after ICV injection or intra-LC microinjection of different doses of gabazine. (B, D) A representative photomicrograph showing …
Figure 9
GABAergic and NEergic systems interact with each other, co-regulate the recovery from midazolam.
(A) Protocol for exploring the influence of knocking down the GABAA-R on the recovery time from midazolam. (B, C) Schematic diagram and the representative photomicrograph showing the position of …
Figure 10
Summary of neural mechanism of rebooting the unconsciousness caused by midazolam.
By using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, we revealed the role of LC-VLPO noradrenergic neural circuit in regulating midazolam-induced altered …
Videos
Video 1
Some of the main experimental videos throughout the study.
Video 2
Some of the main experimental videos throughout the study.
Video 3
Some of the main experimental videos throughout the study.
Video 4
Some of the main experimental videos throughout the study.
Video 5
Some of the main experimental videos throughout the study.
Video 6
Some of the main experimental videos throughout the study.
Video 7
Some of the main experimental videos throughout the study.
Video 8
Some of the main experimental videos throughout the study.
Video 9
Some of the main experimental videos throughout the study.
Video 10
Some of the main experimental videos throughout the study.
Video 11
Some of the main experimental videos throughout the study.
Video 12
Some of the main experimental videos throughout the study.
Video 13
Some of the main experimental videos throughout the study.
Video 14
Some of the main experimental videos throughout the study.
Video 15
Some of the main experimental videos throughout the study.
Video 16
Some of the main experimental videos throughout the study.
Additional files
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Supplementary file 1
Summary table of statistical analysis and reagents conducted throughout the study.
- https://cdn.elifesciences.org/articles/97954/elife-97954-supp1-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/97954/elife-97954-mdarchecklist1-v1.pdf
