The Interaction Between the Ventrolateral Preoptic Nucleus and the Tuberomammillary Nucleus in Regulating the Sleep-Wakefulness Cycle.

Juan Cheng,Ding Ding,Fang Wu,Guihai Chen,Jin Zhang,Liecheng Wang,Sumei Fan,Mingrui Zhang

doi:10.3389/fnins.2020.615854

Abstract

The ventrolateral preoptic nucleus (VLPO) in the anterior hypothalamus and the tuberomammillary nucleus (TMN) in the posterior hypothalamus are critical regions which involve the regulation of sleep-wakefulness flip-flop in the central nervous system. Most of the VLPO neurons are sleep-promoting neurons, which co-express γ-aminobutyric acid (GABA) and galanin, while TMN neurons express histamine (HA), a key wake-promoting neurotransmitter. Previous studies have shown that the two regions are innervated between each other, but how to regulate the sleep-wake cycle are not yet clear. Here, bicuculline (Bic), a GABAA-receptor antagonist, L-glutamate (L-Glu), an excitatory neurotransmitter, and triprolidine (Trip), a HA1 receptor (HRH1) inhibitor, were bilaterally microinjected into TMN or VLPO after surgically implanting the electroencephalogram (EEG) and electromyography (EMG) electrode recording system. Microinjecting L-Glu into VLPO during the night significantly increased the NREM sleep time, and this phenomenon was weakened after selectively blocking GABAA receptors with Bic microinjected into TMN. Those results reveal that VLPO neurons activated, which may inhibit TMN neurons inducing sleep via GABAA receptors. On the contrary, exciting TMN neurons by L-Glu during the day, the wakefulness time was significantly increased. These phenomena were reversed by blocking HRH1 with Trip microinjected into VLPO. Those results reveal that TMN neuron activating may manipulate VLPO neurons via HRH1, and induce wakefulness. In conclusion, VLPO GABAergic neurons and TMN histaminergic neurons may interact with each other in regulating the sleep-wake cycle.

Highlights

The sleep-wake cycle is controlled by homeostasis and circadian rhythm, which regulates the amount, and the time of sleep, respectively (Borbely, 1982)
We found that the non-rapid eye movement (NREM) sleep time was significantly increased after L-Glu was injected into ventral lateral hypothalamus (VLPO), and this phenomenon was weakened after selectively blocking
Compared with the night control group (TMN + aCSF and VLPO + aCSF), the wakefulness time at the 2nd and 3rd h, after L-Glu was injected into VLPO, decreased about 54.0% (p < 0.01) and 37.6% (p < 0.05), respectively (Figure 1B top)

Summary

Introduction

The sleep-wake cycle is controlled by homeostasis and circadian rhythm, which regulates the amount, and the time of sleep, respectively (Borbely, 1982). It is believed that GABAergic neurons in the ventral lateral hypothalamus (VLPO) and central preoptic region are the basis for the occurrence and maintenance of sleep (Sherin et al, 1996; Saper et al, 2010). More than 85% of the neurons in the VLPO region are GABAergic neurons, which co-express the inhibitory neurotransmitters GABA and galanin (Sherin et al, 1996, 1998). VLPO neurons send axons to many regions that are implicated in the regulation of wakefulness, including the locus coeruleus (LC), median raphe nuclei, and the tuberomammillary nucleus (TMN) (Saper et al, 2010; Chung et al, 2017)

Methods

Results

Conclusion