Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

  1. Chang-Rui Chen  Is a corresponding author
  2. Yu-Heng Zhong
  3. Shan Jiang
  4. Wei Xu
  5. Lei Xiao
  6. Zan Wang
  7. Wei-Min Qu  Is a corresponding author
  8. Zhi-Li Huang  Is a corresponding author
  1. Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, China
  2. Department of Neurology, The First Hospital of Jilin University, China
7 figures and 1 additional file

Figures

Figure 1 with 1 supplement
C-fos expression during the inactive period versus during the active period and RV retrograde tracing in PVHvglut2 neurons.

(A) Representative images showing co-expression of mCherry in the PVHvglut2 neurons (red) with c-fos immunostaining (green). The merged image is shown in the right panel (yellow). Scale bars: 200 …

Figure 1—source data 1

C-fos expression and RV retrograde tracing of PVHvglut2 neurons.

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Figure 1—figure supplement 1
Monosynaptic inputs to PVHvglut2 neurons.

Typical brain sections showing the source of monosynaptic afferents to PVHvglut2 neurons. The RV infection sites were marked by red rounds. Abbreviations of the brain regions used are as follows: …

PVHvglut2 neurons are preferentially active during wakefulness.

(A) Schematic of the fiber photometry setup and in vivo recording configuration (DM dichroic mirror, PMT photomultiplier tube). (B) Unilateral viral targeting of AAV-EF1α-DIO-GCaMP6f into the PVH, …

Figure 2—source data 1

In vivo fiber photometry and multichannel electrophysiological recordings of PVHvglut2 neurons.

https://cdn.elifesciences.org/articles/69909/elife-69909-fig2-data1-v2.xlsx
Figure 3 with 2 supplements
Chemogenetic activation of PVHvglut2 increases wakefulness.

(A, B) Expression of the AAV injection site in the PVH of vglut2Cre mice. Drawings of overlay mCherry expressing sites in the PVH of vglut2Cre mice (n = 7, indicated with different colors). (C) …

Figure 3—source data 1

Time spent in each stage of PVHvglut2-M3 mice after administration of CNO or saline during the light phase.

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Figure 3—source data 2

Time spent in each stage of PVHvglut2 mice after administration of CNO or saline during the dark phase.

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Figure 3—source data 3

Heart rate, temperature, serum CRH and CORT levels of PVHvglut2-M3 mice.

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Figure 3—figure supplement 1
Chemogenetic activation of PVHvglut2 neurons during the dark phase increases wakefulness.

(A) Time course of wakefulness, NREM sleep, and REM sleep following injection of vehicle or CNO during the dark phase in mice expressing hM3Dq receptor in PVHvglut2 neurons (n = 4). Statistical …

Figure 3—figure supplement 2
Autonomic and endocrine changes after chemogenetic activation of PVHvglut2 neurons.

(A, B) Simultaneous monitoring of heart rate (A) and temperature (B) with implantable telemetry after administration of vehicle or CNO in freely moving mice. Left panel: Mean ± SEM of heart rate and …

Optogenetic activation of PVHvglut2 neurons induces a rapid transition from NREM sleep to wakefulness.

(A) Left: Schematic of optogenetic manipulation of PVHvglut2 neurons and EEG/EMG recordings. Right: ChR2-mCherry expression and location of optical fiber in the PVH. Scale bar: 200 μm. (B) Example …

Figure 4—source data 1

Latencies of transitions and time course in semi-chronic optogenetic experiments of PVHvglut2-ChR2 mice.

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Figure 5 with 2 supplements
PVHvglut2 neurons control arousal through PB and LSv pathways.

(A, E) Left: Schematic diagram showing the location of the optic fiber in the PB and LSv, and EEG/EMG recordings of a vglut2Cre mouse bilaterally injected with AAV-ChR2-mCherry or AAV-mCherry in the …

Figure 5—source data 1

Statistical analysis of whole-brain outputs from PVHvglut2 neurons.

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Figure 5—source data 2

In vitro photostimulation-evoked EPSCs in PB and LSv neurons.

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Figure 5—figure supplement 1
Representative regions with axonal projection from PVHvglut2 neurons.

(A) Schematic of the viral vectors and injection site for AAV-hSyn-DIO-eGFP in vglut2Cre mice. (B) Fluorescence images showing the AAV infection area in the PVH of a vglut2Cre mouse. Scale bars: 200 …

Figure 5—figure supplement 2
Optogenetic activation of PVHvglut2→NTS or PVHvglut2→PVT pathway has no effect on sleep–wake states.

(A, D) Left: Schematic diagram showing the location of the optic fiber in the NTS or PVT and EEG/EMG recordings of a vglut2Cre mouse injected with AAV-DIO-ChR2-mCherry or AAV-DIO-mCherry in the PVH. …

PVHvglut2 neurons exert wakefulness via PVHOT, PVHPDYN and PVHCRH neurons.

(A, D, G) Schematic drawings of the chemogenetic experiment in OTCre mice, PDYNCre mice and CRHCre mice. (B, E, H) Location of hM3Dq expression in PVHOT, PVHPDYN, and PVHCRH neurons. Right panel: …

Figure 6—source data 1

Time spent in each stage of PVHOT-M3 mice, PVHPDYN-M3 mice, and PVHCRH-M3 mice after administration of CNO or saline.

https://cdn.elifesciences.org/articles/69909/elife-69909-fig6-data1-v2.xlsx
Inhibition or ablation of PVHvglut2 neurons induces hypersomnia-like behaviors.

(A) Expression of AAV injection site in the PVH of vglut2Cre mice. (B) Left panel: Location of hM4Di expression in the PVHvglut2 neurons. Right panel: Drawings of overlay mCherry expressing sites in …

Figure 7—source data 1

Time spent in each stage of PVHvglut2-m4 mice after administration of CNO or saline and time spent in each stage of PVH vglut2-Caspase3 mice.

https://cdn.elifesciences.org/articles/69909/elife-69909-fig7-data1-v2.xlsx

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