Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

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 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 h, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

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Paraventricular hypothalamic nucleus are essential for arousal promotion and maintenance

10.21203/rs.3.rs-140209/v1 ◽

2021 ◽

Author(s):

Zhi-Li Huang ◽

Chang-Rui Chen ◽

Yu-Heng Zhong ◽

Shan Jiang ◽

Wei Xu ◽

...

Keyword(s):

Nrem Sleep ◽

Neural Circuitry ◽

Lateral Septum ◽

Hypothalamic Nucleus ◽

Population Activity ◽

Daytime Functioning ◽

Paraventricular Hypothalamic Nucleus ◽

Clinical Observations ◽

Electrophysiological Recordings

Abstract Adequate wakefulness is fundamental for proper daytime functioning. Clinical observations indicate that the paramedian region of the hypothalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Here, we found that inhibition of PVHvglut2 neurons induced 3-h increase of NREM sleep. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH neuronal activation also exerted wakefulness. Photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from NREM to wakefulness. Furthermore, using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we find arousal-dependent increases in population activity of PVHvglut2 neurons. Most importantly, ablation of PVHvglut2 neurons dramatically led mice to hypersomnia-like behaviors. These results demonstrate that PVHvglut2 neurons are essential for physiologic arousal in the hypothalamus.

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Convergent influence of the central nucleus of the amygdala and the paraventricular hypothalamic nucleus upon brainstem autonomic neurons as revealed by c-fos expression and anatomical tracing

Journal of Neuroscience Research ◽

10.1002/jnr.490420612 ◽

1995 ◽

Vol 42 (6) ◽

pp. 835-845 ◽

Cited By ~ 38

Author(s):

T. Petrov ◽

T. L. Krukoff ◽

J. H. Jhamandas

Keyword(s):

Central Nucleus ◽

Hypothalamic Nucleus ◽

Paraventricular Hypothalamic Nucleus ◽

Autonomic Neurons ◽

Fos Expression

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Vestibular-mediated increase in central serotonin plays an important role in hypergravity-induced hypophagia in rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00515.2010 ◽

2010 ◽

Vol 109 (6) ◽

pp. 1635-1643 ◽

Cited By ~ 17

Author(s):

Chikara Abe ◽

Kunihiko Tanaka ◽

Chihiro Iwata ◽

Hironobu Morita

Keyword(s):

Area Postrema ◽

Vestibular Nucleus ◽

Central Nucleus ◽

Medial Vestibular Nucleus ◽

Hypothalamic Nucleus ◽

Solitary Tract ◽

Afferent Pathway ◽

Vestibular Input ◽

Paraventricular Hypothalamic Nucleus ◽

Fos Expression

Exposure to a hypergravity environment induces acute transient hypophagia, which is partially restored by a vestibular lesion (VL), suggesting that the vestibular system is involved in the afferent pathway of hypergravity-induced hypophagia. When rats were placed in a 3-G environment for 14 days, Fos-containing cells increased in the paraventricular hypothalamic nucleus, the central nucleus of the amygdala, the medial vestibular nucleus, the raphe nucleus, the nucleus of the solitary tract, and the area postrema. The increase in Fos expression was completely abolished or significantly suppressed by VL. Therefore, these regions may be critical for the initiation and integration of hypophagia. Because the vestibular nucleus contains serotonergic neurons and because serotonin (5-HT) is a key neurotransmitter in hypophagia, with possible involvement in motion sickness, we hypothesized that central 5-HT increases during hypergravity and induces hypophagia. To examine this proposition, the 5-HT concentrations in the cerebrospinal fluid were measured when rats were reared in a 3-G environment for 14 days. The 5-HT concentrations increased in the hypergravity environment, and these increases were completely abolished in rats with VL. Furthermore, a 5-HT2A antagonist (ketanserin) significantly reduced 3-G (120 min) load-induced Fos expression in the medial vestibular nucleus, and chronically administered ketanserin ameliorated hypergravity-induced hypophagia. These results indicate that hypergravity induces an increase in central 5-HT via the vestibular input and that this increase plays a significant role in hypergravity-induced hypophagia. The 5-HT2A receptor is involved in the signal transduction of hypergravity stress in the vestibular nucleus.

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Electroacupuncture Reduces Stress-Induced Expression of c-Fos in the Brain of the Rat

The American Journal of Chinese Medicine ◽

10.1142/s0192415x04002405 ◽

2004 ◽

Vol 32 (05) ◽

pp. 795-806 ◽

Cited By ~ 28

Author(s):

Hye-Jung Lee ◽

Bombi Lee ◽

Sun-Hye Choi ◽

Dae-Hyun Hahm ◽

Mi-Rye Kim ◽

...

Keyword(s):

Immobilization Stress ◽

Plasma Catecholamines ◽

Inhibitory Effect ◽

Lateral Septum ◽

Hypothalamic Nucleus ◽

Amygdaloid Nucleus ◽

Bed Nucleus ◽

Fos Expression ◽

Medial Amygdaloid Nucleus ◽

The Brain

We have previously shown that electroacupuncture (EA) at Shaohai and Neiguan ( HT 3- PC 6) points significantly attenuated stress-induced peripheral responses, including increases in blood pressure, heart rate and plasma catecholamines. In this study, we examined the central effect of EA on the expression of c-fos, one of the immediate-early genes in the brain of rats subjected to immobilization stress. Immobilization stress (180 minutes) preferentially produced a significant increase in Fos-like immunoreactivity (FLI) in stress-relevant regions including the paraventricular hypothalamic nucleus (PVN), arcuate nucleus (ARN), supraoptic nucleus (SON), suprachiasmatic nucleus (SCN), medial amygdaloid nucleus (AMe), bed nucleus of the stria terminalis (BST), hippocampus, lateral septum (LS), nucleus accumbens, and the locus coeruleus (LC). EA (3 Hz, 0.2 ms rectangular pulses, 20 mA) at HT 3- PC 6 on the heart and pericardium channels for 30 minutes during stress, significantly attenuated stress-induced FLI in the parvocellular PVN, SON, SCN, AMe, LS and the LC. However, EA stimulations at HT 3- PC 6 had no effect on FLI in the magnocelluar PVN, ARN, BST or the hippocampus. EA stimulation at HT 3- PC 6 had a greater inhibitory effect on stress-induced FLI than that at TE 5- LI 11, the triple energizer and large intestine meridian, or non-acupoints. These results demonstrated that EA attenuated stress-induced c-fos expression in brain areas. These results suggest that decreased c-fos expression in hypothalamic and LC neurons, among stress-related areas, may reflect the integrative action of acupuncture in stress response.

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Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in human and mice

10.1101/2021.05.11.443607 ◽

2021 ◽

Author(s):

Zhi-Li Huang ◽

Chang-Rui Chen ◽

Yu-Heng Zhong ◽

Shan Jiang ◽

Wei Xu ◽

...

Keyword(s):

Paraventricular Nucleus ◽

Essential Role ◽

Physiological Arousal ◽

Neural Circuitry ◽

Electrophysiological Recording ◽

Hypothalamic Nucleus ◽

Neuronal Activation ◽

Paraventricular Hypothalamic Nucleus

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infections or tumorigenesis. HD was traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesion of a single, even two or more wake-promoting nucleuses simultaneously did not exert serious HD. The specific nucleus and neural circuitry for HD remain unknown. Here, we observed that three patients with lesions around the paraventricular nucleus 23 of the hypothalamus (PVH) showed hypersomnolence lasting more than 20 h per day and their excessive sleep decreased with the recovery of the PVH area. Therefore, we hypothesized that the PVH might play an essential role in the occurrence of HD. Using multichannel electrophysiological recording and fiber photometry, we found that PVHvglut2 neurons were preferentially active during wakefulness. Chemogenetic activation of PVHvglut2 neurons potently induced 9-h wakefulness, and PVHCRH, PVHPDYN and PVHOT neuronal activation also exerted wakefulness. Most importantly, ablation of PVHvglut2 neurons drastically induced hypersomnia-like behaviors (30.6% reduction in wakefulness). These results indicate that dysfunctions of the PVH is crucial for physiological arousal and pathogenesis underlying HD.

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