Dysfunctions of the Paraventricular Hypothalamic Nucleus Induce Hypersomnia in Mice

Overview

Journal Elife

Specialty Biology

Date 2021 Nov 17

PMID 34787078

Citations 21

Authors

Chang-Rui Chen

Yu-Heng Zhong

Shan Jiang

Wei Xu

Lei Xiao

Zan Wang

Wei-Min Qu

Zhi-Li Huang

Affiliations

Soon will be listed here.

Abstract

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVH neurons were most active during wakefulness. Chemogenetic activation of PVH neurons induced wakefulness for 9 hr, and photostimulation of PVH→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVH neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

Citing Articles

The central regulatory effects of acupuncture in treating primary insomnia: a review.

Yao L, Liu Y, Li M, Zheng H, Sun M, He M Front Neurol. 2024; 15:1406485.

PMID: 39719980 PMC: 11666528. DOI: 10.3389/fneur.2024.1406485.

Hypothalamic corticotropin-releasing hormone neurons modulate sevoflurane anesthesia and the post-anesthesia stress responses.

Jiang S, Chen L, Qu W, Huang Z, Chen C Elife. 2024; 12.

PMID: 39526880 PMC: 11554309. DOI: 10.7554/eLife.90191.

Protective role of aconitate decarboxylase 1 in neuroinflammation-induced dysfunctions of the paraventricular thalamus and sleepiness.

Chang J, Li Z, Yuan H, Wang X, Xu J, Yang P Commun Biol. 2024; 7(1):1484.

PMID: 39523388 PMC: 11551151. DOI: 10.1038/s42003-024-07215-0.

Oxytocin Protects Nigrostriatal Dopamine Signal via Activating GABAergic Circuit in the MPTP-Induced Parkinson's Disease Model.

Wang Y, Xu H, Chen S, Chen J, Zheng Q, Ma Y Adv Sci (Weinh). 2024; 11(36):e2310244.

PMID: 39099429 PMC: 11423065. DOI: 10.1002/advs.202310244.

The Changed Nocturnal Sleep Structure and Higher Anxiety, Depression, and Fatigue in Patients with Narcolepsy Type 1.

Yu J, Zhang Y, Cai L, Sun Q, Li W, Zhou J Nat Sci Sleep. 2024; 16:725-735.

PMID: 38873239 PMC: 11170032. DOI: 10.2147/NSS.S452665.

References

Zhong Y, Jiang S, Qu W, Zhang W, Huang Z, Chen C . Saikosaponin a promotes sleep by decreasing neuronal activities in the lateral hypothalamus. J Sleep Res. 2021; 31(2):e13484. DOI: 10.1111/jsr.13484. View

Qiu M, Chen M, Fuller P, Lu J . Stimulation of the Pontine Parabrachial Nucleus Promotes Wakefulness via Extra-thalamic Forebrain Circuit Nodes. Curr Biol. 2016; 26(17):2301-12. PMC: 5025760. DOI: 10.1016/j.cub.2016.07.054. View

Xiao L, Priest M, Nasenbeny J, Lu T, Kozorovitskiy Y . Biased Oxytocinergic Modulation of Midbrain Dopamine Systems. Neuron. 2017; 95(2):368-384.e5. PMC: 7881764. DOI: 10.1016/j.neuron.2017.06.003. View

Xu Y, Wu Z, Sun H, Zhu Y, Ran Kim E, Lowell B . Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab. 2013; 18(6):860-70. PMC: 3880549. DOI: 10.1016/j.cmet.2013.11.003. View

Ono D, Mukai Y, Hung C, Chowdhury S, Sugiyama T, Yamanaka A . The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus. Sci Adv. 2020; 6(45). PMC: 7673716. DOI: 10.1126/sciadv.abd0384. View

Daviu N, Fuzesi T, Rosenegger D, Rasiah N, Sterley T, Peringod G . Paraventricular nucleus CRH neurons encode stress controllability and regulate defensive behavior selection. Nat Neurosci. 2020; 23(3):398-410. DOI: 10.1038/s41593-020-0591-0. View

Morton A . A quantitative analysis of the normal neuron population of the hypothalamic magnocellular nuclei in man and of their projections to the neurohypophysis. J Comp Neurol. 1969; 136(2):143-57. DOI: 10.1002/cne.901360203. View

Bollu P, Manjamalai S, Thakkar M, Sahota P . Hypersomnia. Mo Med. 2018; 115(1):85-91. PMC: 6139790. View

Carter M, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S . Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci. 2010; 13(12):1526-33. PMC: 3174240. DOI: 10.1038/nn.2682. View

10.

Li J, Liao X, Zhang J, Wang M, Yang N, Zhang J . Primary Auditory Cortex is Required for Anticipatory Motor Response. Cereb Cortex. 2017; 27(6):3254-3271. DOI: 10.1093/cercor/bhx079. View

11.

Kroeger D, Ferrari L, Petit G, Mahoney C, Fuller P, Arrigoni E . Cholinergic, Glutamatergic, and GABAergic Neurons of the Pedunculopontine Tegmental Nucleus Have Distinct Effects on Sleep/Wake Behavior in Mice. J Neurosci. 2017; 37(5):1352-1366. PMC: 5296799. DOI: 10.1523/JNEUROSCI.1405-16.2016. View

12.

Lu J, Sherman D, Devor M, Saper C . A putative flip-flop switch for control of REM sleep. Nature. 2006; 441(7093):589-94. DOI: 10.1038/nature04767. View

13.

Xu S, Yang H, Menon V, Lemire A, Wang L, Henry F . Behavioral state coding by molecularly defined paraventricular hypothalamic cell type ensembles. Science. 2020; 370(6514). DOI: 10.1126/science.abb2494. View

14.

Kondoh K, Lu Z, Ye X, Olson D, Lowell B, Buck L . A specific area of olfactory cortex involved in stress hormone responses to predator odours. Nature. 2016; 532(7597):103-6. PMC: 5094457. DOI: 10.1038/nature17156. View

15.

Ziegler D, Cullinan W, Herman J . Organization and regulation of paraventricular nucleus glutamate signaling systems: N-methyl-D-aspartate receptors. J Comp Neurol. 2005; 484(1):43-56. DOI: 10.1002/cne.20445. View

16.

Windle R, Kershaw Y, Shanks N, Wood S, Lightman S, Ingram C . Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity. J Neurosci. 2004; 24(12):2974-82. PMC: 6729832. DOI: 10.1523/JNEUROSCI.3432-03.2004. View

17.

Manaye K, Lei D, Tizabi Y, Davila-Garcia M, Mouton P, Kelly P . Selective neuron loss in the paraventricular nucleus of hypothalamus in patients suffering from major depression and bipolar disorder. J Neuropathol Exp Neurol. 2005; 64(3):224-9. DOI: 10.1093/jnen/64.3.224. View

18.

Pedersen N, Ferrari L, Venner A, Wang J, Abbott S, Vujovic N . Supramammillary glutamate neurons are a key node of the arousal system. Nat Commun. 2017; 8(1):1405. PMC: 5680228. DOI: 10.1038/s41467-017-01004-6. View

19.

Sterley T, Baimoukhametova D, Fuzesi T, Zurek A, Daviu N, Rasiah N . Social transmission and buffering of synaptic changes after stress. Nat Neurosci. 2018; 21(3):393-403. DOI: 10.1038/s41593-017-0044-6. View

20.

Lu J, Jhou T, Saper C . Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J Neurosci. 2006; 26(1):193-202. PMC: 6674316. DOI: 10.1523/JNEUROSCI.2244-05.2006. View