The restricted hypothalamic distribution of Hcrt neurons appears to be similar among different species. Studies have confirmed the presence of Hcrt neurons in the human and monkey, various strains of mice, rats, and hamsters; in other mammals such as the cat, sheep, and pig; in the chicken, three species of amphibians, and the zebrafish.
In the human brain, Hcrt-immunoreactive neurons are localized to the perifornical area and DMH, with few neurons seen in the LHA12,43 and Hcrt-immunoreactive axons are as widespread as those seen in rodents (see Section 6). In the monkey hypothalamus, the location of Hcrt neurons and the distribution of Hcrt axons is roughly similar to that seen in the rat, with Hcrt-immunoreactive neurons in the perifornical area and LHA and, to a lesser extent, in the DMH.44 In the cat brain, Hcrt-1-immunoreactive neurons are present in the tuberal hypothalamus and have a roughly similar distribution to that seen in rodents, with the greatest concentrations of neurons seen dorsal and lateral to the fornix, although the neurons are slightly more widely scattered than in the rat with several neurons extending in the medial direction to the periventricular region and a few neurons as far ventral as the arcuate nucleus.45,46 In the sheep hypothalamus, the distribution of Hcrt1-immunoreactive neurons differed from the rodent brain in that many Hcrt neurons were found in the DMH and perifornical area with fewer neurons scattered in the LHA.47 Hcrt neurons in the Siberian and Syrian hamster, visualized by Hcrt1 immunohistochemistry, were present in the perifornical area and LHA. The morphology of Hcrt neurons in the hamster were piriform with 2-3 primary dendrites.48,49 In the pig, Hcrt1- and Hcrt2-immunoreactive neurons have a similar distribution in the perifornical area and LHA.50
The Hcrt system has also been studied in non-mammalian vertebrates. In the frog Rana ridibunda, Hcrt2-immunoreactive neurons were detected in the diencephalon, with a high density of neurons found in the SCN and fewer neurons seen in the preoptic area, and the magnocellular and ventral hypothalamic nuclei.51 The frog SCN is likely not directly analogous of the rodent SCN, since NPY neurons are found in the frog SCN whereas only NPY-positive fibers are seen in the rat SCN.52 In the bullfrog Rana catesbeiana, additional Hcrt1-immunoreactive neurons were seen in the pituitary gland where they colocalized with frog prolactin-immunoreactivity.53 In the toad Xenopus laevis, Hcrt neurons were found in the ventral hypothalamic nucleus. The distribution of immunoreactive fibers was widespread in the brain, similar to that seen in mammals.54 In the chicken, hcrt mRNA and Hcrt immunoreactivity was seen in neurons in the periventricular hypothalamus and LHA.55 The zebrafish (Danio rerio) was found to have two clusters of Hcrt-immunoreactive neurons: an anterior hypothalamic cluster and a preoptic cluster. However, only the hypothalamic cluster was considered to contain true Hcrt neurons, as mRNA was undetectable by in situ hybridization in the preoptic cluster.56 Hcrt-immunoreactive axons were found to terminate among cholinergic and monoaminergic cells groups and Hcrt neurons were innervated by serotonergic, catecholaminergic, histaminergic and cholinergic fibers.56
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