Nuclear organization of serotonergic neurons in the brainstems of a lar gibbon and a chimpanzee.

In the current study, we detail, through the analysis of immunohistochemically stained sections, the morphology and nuclear parcellation of the serotonergic neurons present in the brainstem of a lar gibbon and a chimpanzee. In general, the neuronal morphology and nuclear organization of the serotonergic system in the brains of these two species of apes follow that observed in a range of Eutherian mammals and are specifically very similar to that observed in other species of primates. In both of the apes studied, the serotonergic nuclei could be readily divided into two distinct groups, a rostral and a caudal cluster, which are found from the level of the decussation of the superior cerebellar peduncle to the spinomedullary junction. The rostral cluster is comprised of the caudal linear, supralemniscal, and median raphe nuclei, as well as the six divisions of the dorsal raphe nuclear complex. The caudal cluster contains several distinct nuclei and nuclear subdivisions, including the raphe magnus nucleus and associated rostral and caudal ventrolateral (CVL) serotonergic groups, the raphe pallidus, and raphe obscurus nuclei. The one deviation in organization observed in comparison to other primate species is an expansion of both the number and distribution of neurons belonging to the lateral division of the dorsal raphe nucleus in the chimpanzee. It is unclear whether this expansion occurs in humans, thus at present, this expansion sets the chimpanzee apart from other primates studied to date.

Nuclear organization of catecholaminergic neurons in the brains of a lar gibbon and a chimpanzee.

Using tyrosine hydroxylase immunohistochemistry, we describe the nuclear parcellation of the catecholaminergic system in the brains of a lar gibbon (Hylobates lar) and a chimpanzee (Pan troglodytes). The parcellation of catecholaminergic nuclei in the brains of both apes is virtually identical to that observed in humans and shows very strong similarities to that observed in mammals more generally, particularly other primates. Specific variations of this system in the apes studied include an unusual high-density cluster of A10dc neurons, an enlarged retrorubral nucleus (A8), and an expanded distribution of the neurons forming the dorsolateral division of the locus coeruleus (A4). The additional A10dc neurons may improve dopaminergic modulation of the extended amygdala, the enlarged A8 nucleus may be related to the increased use of communicative facial expressions in the hominoids compared to other primates, while the expansion of the A4 nucleus appears to be related to accelerated evolution of the cerebellum in the hominoids compared to other primates. In addition, we report the presence of a compact division of the locus coeruleus proper (A6c), as seen in other primates, that is not present in other mammals apart from megachiropteran bats. The presence of this nucleus in primates and megachiropteran bats may reflect homology or homoplasy, depending on the evolutionary scenario adopted. The fact that the complement of homologous catecholaminergic nuclei is mostly consistent across mammals, including primates, is advantageous for the selection of model animals for the study of specific dysfunctions of the catecholaminergic system in humans.

Nuclear organization of orexinergic neurons in the hypothalamus of a lar gibbon and a chimpanzee.

Employing orexin-A immunohistochemical staining we describe the nuclear parcellation of orexinergic neurons in the hypothalami of a lar gibbon and a chimpanzee. The clustering of orexinergic neurons within the hypothalamus and the terminal networks follow the patterns generally observed in other mammals, including laboratory rodents, strepsirrhine primates and humans. The orexinergic neurons were found within three distinct clusters in the ape hypothalamus, which include the main cluster, zona incerta cluster and optic tract cluster. In addition, the orexinergic neurons of the optic tract cluster appear to extend to a more rostral and medial location than observed in other species, being observed in the tuberal region in the anterior ventromedial aspect of the hypothalamus. While orexinergic terminal networks were observed throughout the brain, high density terminal networks were observed within the hypothalamus, medial and intralaminar nuclei of the dorsal thalamus, and within the serotonergic and noradrenergic regions of the midbrain and pons, which is typical for mammals. The expanded distribution of orexinergic neurons into the tuberal region of the ape hypothalamus, is a feature that needs to be investigated in other primate species, but appears to correlate with orexin gene expression in the same region of the human hypothalamus, but these neurons are not revealed with immunohistochemical staining in humans. Thus, it appears that apes have a broader distribution of orexinergic neurons compared to other primate species, but that the neurons within this extension of the optic tract cluster in humans, while expressing the orexin gene, do not produce the neuropeptide.

Distribution of cholinergic neurons in the brains of a lar gibbon and a chimpanzee.

Using choline acetyltransferase immunohistochemistry, we describe the nuclear parcellation of the cholinergic system in the brains of two apes, a lar gibbon (Hylobates lar) and a chimpanzee (Pan troglodytes). The cholinergic nuclei observed in both apes studied are virtually identical to that observed in humans and show very strong similarity to the cholinergic nuclei observed in other primates and mammals more generally. One specific difference between humans and the two apes studied is that, with the specific choline acetyltransferase antibody used, the cholinergic pyramidal neurons observed in human cerebral cortex were not labeled. When comparing the two apes studied and humans to other primates, the presence of a greatly expanded cholinergic medullary tegmental field, and the presence of cholinergic neurons in the intermediate and dorsal horns of the cervical spinal cord are notable variations of the distribution of cholinergic neurons in apes compared to other primates. These neurons may play an important role in the modulation of ascending and descending neural transmissions through the spinal cord and caudal medulla, potentially related to the differing modes of locomotion in apes compared to other primates. Our observations also indicate that the average soma volume of the neurons forming the laterodorsal tegmental nucleus (LDT) is larger than those of the pedunculopontine nucleus (PPT) in both the lar gibbon and chimpanzee. This variability in soma volume appears to be related to the size of the adult derivatives of the alar and basal plate across mammalian species.

The distribution, number, and certain neurochemical identities of infracortical white matter neurons in a chimpanzee (Pan troglodytes) brain.

We examined the number, distribution, and immunoreactivity of the infracortical white matter neuronal population, also termed white matter interstitial cells (WMICs), throughout the telencephalic white matter of an adult female chimpanzee. Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most numerous and dense close to the inner border of cortical layer VI, decreasing significantly in density with depth in the white matter. Stereological analysis of NeuN-immunopositive cells revealed an estimate of approximately 137.2 million WMICs within the infracortical white matter of the chimpanzee brain studied. Immunostaining revealed subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS, approximately 14.4 million in number), calretinin (CR, approximately 16.7 million), very few WMICs containing parvalbumin (PV), and no calbindin-immunopositive neurons. The nNOS, CR, and PV immunopositive WMICs, possibly all inhibitory neurons, represent approximately 22.6% of the total WMIC population. As the white matter is affected in many cognitive conditions, such as schizophrenia, autism, epilepsy, and also in neurodegenerative diseases, understanding these neurons across species is important for the translation of findings of neural dysfunction in animal models to humans. Furthermore, studies of WMICs in species such as apes provide a crucial phylogenetic context for understanding the evolution of these cell types in the human brain.

Birth of rhesus macaque (Macaca mulatta) infants after in vitro fertilization and gestation in female rhesus or pigtailed (Macaca nemestrina) macaques.

A study was conducted to assess the possibility of using pigtailed macaques (Macaca nemestrina) as recipients for rhesus macaque (Macaca mulatta) embryos. A total of 250 oocytes were collected from 11 rhesus monkeys during 12 follicular aspirations. We performed 15 embryo transfers with two embryos each into rhesus recipients, which resulted in eight pregnancies, of which two were lost during the second trimester. Among the remaining six pregnant rhesus macaques, two were carrying twins, resulting in the birth of eight infants. Twelve transfers of rhesus embryos into pigtailed macaques resulted in one pregnancy and the birth of one infant. Fetal growth and development were monitored by monthly ultrasound examinations, during which biparietal measurements were taken and compared with those derived from 22 pregnant control monkeys. In vitro fertilization-derived singletons tended to develop faster than did twins and naturally conceived control singletons during the initial months of pregnancy and weighed more at birth than did twins. There were pronounced morphologic changes in the placenta of the rhesus that developed in the female pigtailed macaque. These included an irregular shape, elevated placenta-to-birth-weight ratio, and an abnormal length and diameter of the umbilical cord. Histologic analyses of the rhesus-pigtailed placenta showed evidence of maternal-placental floor infarction and thrombosis of the spiral artery with resulting infarction of the villi. These results demonstrate that pigtailed macaques can carry rhesus fetuses to term, but further studies are necessary to determine the cause of the decreased pregnancy rates and observed placental abnormalities.