The hypothalamic orexin (hypocretin) neuropeptides are associated with the
regulation of sleep and feeding, and disturbances in orexinergic neurotrans
mission lead to a narcoleptic phenotype. Histamine has also been shown to p
lay a role in the regulation of sleep and feeding. Therefore, we studied th
e relationship between the orexin and histamine systems of the CNS using el
ectrophysiology, immunocytochemistry, and the reverse transcriptase (RT)-PC
R method.
Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary n
eurons and increased their firing rate via an action on postsynaptic recept
ors. The depolarization was associated with a small decrease in input resis
tance and was likely caused by activation of both the electrogenic Na+/Ca2 exchanger and a Ca2+ current. In a single-cell RT-PCR study using primers
for the two orexin receptors, we found that most tuberomammillary neurons e
xpress both receptors and that the expression of the orexin-2 receptor is s
tronger than that of the orexin-1 receptor. Immunocytochemical studies show
that the histamine and orexin neurons are often located very close to each
other. The contacts between these two types of neurons seem to be reciproc
al, because the orexin neurons are heavily innervated by histaminergic axon
s. These results suggest a functional connection between the two population
s of hypothalamic neurons and that they may cooperate in the regulation of
rapid-eye-movement sleep and feeding.