Glutamate Activates the Histaminergic Tuberomammillary Nucleus and Increases Wakefulness in Rats. (10th August 2019)

• Record Type: Journal Article
• Authors: Yin, Dou; Dong, Hui; Wang, Tian-Xiao; Hu, Zhen-Zhen; Cheng, Neng-Neng; Qu, Wei-Min; Huang, Zhi-Li
• Is Part Of: Neuroscience. Volume 413(2019)
• Page Start: 86
• Page End: 98
• Publication Date: 2019-08-10
• Subjects: ACSF artificial cerebrospinal fluid -- AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- AP anteroposterior -- DHK dihydrokainate -- DV dorsoventral -- EEG electroencephalogram -- EMG electromyogram -- GLT-1 glutamate transporter 1 -- H1R H1 receptor -- H2R H2 receptor -- H3R H3 receptor -- H4R H4 receptor -- LR left–right -- MCH melanin-concentrating hormone -- NMDA N-methyl-D-aspartate -- NREM non-rapid eye movement -- PBS phosphate-buffered saline -- PFC prefrontal cortex -- PLSD probable least-squares difference -- REM rapid eye movement -- TMN tuberomammillary nucleus; glutamate -- sleep -- wakefulness -- histamine -- NMDA; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.05.032
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: Glutamate is the major excitatory neurotransmitter in the brain and plays an essential role in regulating wakefulness. Histaminergic neurons, which are exclusively localized in the tuberomammillary nucleus (TMN) of the hypothalamus, have a pivotal role in the regulation of sleep–wake patterns by sending widespread projections into many brain areas implicated in sleep–wake control. The role of glutamate in histaminergic neurons within the TMN and the resulting sleep–wake profile remains unknown. We found that glutamate, NMDA, AMPA or dihydrokainate, a glutamate-uptake inhibitor, dose-dependently increased wakefulness when microinjected into the rat TMN. Glutamate, NMDA, and AMPA also increased the firing rate of action potentials in TMN histaminergic neurons. The arousal-promoting effect of glutamate was inhibited by NMDA and histamine H1 receptor antagonists. Furthermore, MK-801, an NMDA receptor antagonist, inhibited the firing rate of histaminergic neurons and increased non-rapid eye movement sleep after microinjection into rat TMN. Taken together, these findings demonstrated that glutamate activated histaminergic neurons in the TMN and increased wakefulness in rats, possibly via the action of NMDA and histamine H1 receptors. Highlights: Glutamate and its receptor agonist NMDA and AMPA increase wakefulness in rats. Glutamate, NMDA and AMPA activate the histaminergic neurons in TMN. The effect of glutamate was inhibited by NMDAR and histamine H1 R antagonists.