Histamine regulates activities of neurons in the ventrolateral preoptic nucleus.
The neurons responsible for the onset of sleep are thought to be located in the ventrolateral preoptic nucleus (VLPO), which receives a dense histaminergic innervation from the tuberomammillary nucleus (TMN). Yet, the role of histamine in the VLPO remains unclear. Here we report that microinjection of histamine into the VLPO increases the motor activity of rats. Moreover, a bath application of histamine to acute brain slices inhibits the majority of VLPO neurons, which are also inhibited by noradrenaline. Histamine hyperpolarizes the membrane potential and lowers the firing rate. These effects are associated with an increase in the frequency but not in the amplitude of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic currents, and are blocked by gabazine or tetrodotoxin, indicating an indirect action. Conversely, on the noradrenaline-excited VLPO neurons, histamine depolarizes the membrane potential and increases the firing rate via activation of H(1) and H(2) subtype histamine receptors. Moreover, histamine-induced depolarization persists in the presence of gabazine or tetrodotoxin, indicating a direct action. Based on these findings, we propose that in the VLPO, noradrenaline-inhibited neurons may normally be under the inhibitory control of noradrenaline-excited neurons. By facilitating the inhibitory control of the noradrenaline-excited neurons, histamine may inhibit the noradrenaline-inhibited neurons, resulting in excitation of histamine-releasing neurons in the TMN through disinhibition. This effect of histamine in the VLPO may contribute to the maintenance of wakefulness.
Liu
Yu-Wei
YW
Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103-2714, USA.
Li
Jing
J
Ye
Jiang-Hong
JH
D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects* / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology*
D018756:GABA Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; D011968:Receptors, Histamine; D013779:Tetrodotoxin; D006632:Histamine; C049853:gabazine; D009638:Norepinephrine