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

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 gamma-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(A)-receptor antagonist, L-glutamate (L-Glu), an excitatory neurotransmitter, and triprolidine (Trip), a HA(1) 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 GABA(A) receptors with Bic microinjected into TMN. Those results reveal that VLPO neurons activated, which may inhibit TMN neurons inducing sleep via GABA(A) 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.