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Status |
Public on Jul 20, 2024 |
Title |
Astrocytes modulate a specific paraventricular thalamus-prefrontal cortex projection to enhance consciousness recovery from sevoflurane anesthesia in mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Previous studies have proved that astrocytes may be a key neural substrate that regulates wakefulness and consciousness recovery from general anesthesia, while the exact molecular target in astrocytes is still unclear. Using virus injection and in vivo fiber photometry in mice, we found both activating astrocytes and knocking down astrocytic Kir4.1 in paraventricular thalamus (PVT) promotes the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVTGRM and PVTChAT neurons. Patch-clamp recording results proved that Astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly works on PVTChAT neurons. Moreover, we found that PVTChAT neurons project mainly to the mPFC. This specific paraventricular thalamus to prefrontal cortex projection is involved in recovery of consciousness from sevoflurane anesthesia indirectly through modulation of astrocytes. In summary, our findings support the novel conception that the volatile anesthetic sevoflurane can inhibit PVT astrocytic Kir 4.1 to maintain and/or increase neuronal firing of PVTChAT neurons, which mainly projects to mPFC and promotes consciousness recovery from anesthesia.
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Overall design |
Using virus injection and in vivo fiber photometry in mice, we found both activating astrocytes and knocking down astrocytic Kir4.1 in paraventricular thalamus (PVT) promotes the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVTGRM and PVTChAT neurons. Patch-clamp recording results proved that Astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly works on PVTChAT neurons. Moreover, using virological tracer, we found that PVTChAT neurons project mainly to the mPFC.
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Contributor(s) |
Zhao Y, Ou M, Liu J, Jiang J, Zhang D, Yang Y, Ke B, Wu Y, Jiang R, Mulkey DK, Zhu T, Zhou C, Hemmings HC Jr |
Citation missing |
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Submission date |
Aug 08, 2023 |
Last update date |
Jul 20, 2024 |
Contact name |
Cheng Zhou |
E-mail(s) |
zhouc1985@gmail.com
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Organization name |
West China Hospital of Sichuan University
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Street address |
No District, Chengdu, Sichuan Province. 37 Guoxue Lane, Wuhou
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City |
Chengdu |
State/province |
Sichuan |
ZIP/Postal code |
610000 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA1003482 |
Supplementary file |
Size |
Download |
File type/resource |
GSE240388_RAW.tar |
244.3 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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