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

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

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.615854

DOI=10.3389/fnins.2020.615854

ISSN=1662-453X

ABSTRACT=<p>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 GABA<sub><italic>A</italic></sub>-receptor antagonist, <sc>L</sc>-glutamate (<sc>L</sc>-Glu), an excitatory neurotransmitter, and triprolidine (Trip), a HA<sub>1</sub> receptor (HRH<sub>1</sub>) inhibitor, were bilaterally microinjected into TMN or VLPO after surgically implanting the electroencephalogram (EEG) and electromyography (EMG) electrode recording system. Microinjecting <sc>L</sc>-Glu into VLPO during the night significantly increased the NREM sleep time, and this phenomenon was weakened after selectively blocking GABA<sub><italic>A</italic></sub> receptors with Bic microinjected into TMN. Those results reveal that VLPO neurons activated, which may inhibit TMN neurons inducing sleep via GABA<sub><italic>A</italic></sub> receptors. On the contrary, exciting TMN neurons by <sc>L</sc>-Glu during the day, the wakefulness time was significantly increased. These phenomena were reversed by blocking HRH<sub>1</sub> with Trip microinjected into VLPO. Those results reveal that TMN neuron activating may manipulate VLPO neurons via HRH<sub>1</sub>, and induce wakefulness. In conclusion, VLPO GABAergic neurons and TMN histaminergic neurons may interact with each other in regulating the sleep-wake cycle.</p>