Orexinergic neurons in the hypothalami of an Asiatic lion, an African lion, and a Southeast African cheetah

Abstract

Employing orexin-A immunohistochemistry, we describe the distribution, morphology, and nuclear parcellation of orexinergic neurons within the hypothalami of an Asiatic lion (Panthera leo subsp. persica), an African lion (Panthera leo subsp. melanochaita), and a Southeast African cheetah (Acinonyx jubatus subsp. jubatus). In all three felids, the clustering of large, bipolar, and multipolar hypothalamic orexinergic neurons primarily follows the pattern observed in other mammals. The orexinergic neurons were found, primarily, to form three distinct clusters-the main, zona incerta, and optic tract clusters. In addition, large orexinergic neurons were observed in the ventromedial supraoptic region of the hypothalamus, where they are not typically observed in other species. As has been observed in cetartiodactyls and the African elephant, a cluster of small, multipolar orexinergic neurons, the parvocellular cluster, was observed in the medial zone of the hypothalamus in all three felids, although this parvocellular cluster has not been reported in other carnivores. In both subspecies of lions, but not the cheetah, potential orexin-immunopositive neurons were observed in the paraventricular hypothalamic nucleus, supraoptic nucleus, the lateral part of the retrochiasmatic area, and the inner layer of the median eminence. The distribution and parcellation of orexinergic neurons in the hypothalami of the three felids studied appear to be more complex than observed in many other mammals and for the two subspecies of lion may be even more complex. These findings are discussed in terms of potential technical concerns, phylogenetic variations of this system, and potentially associated functional aspects of the orexinergic system.

Nuclear parcellation and numbers of orexinergic neurons in five species of larger brained birds

“…OxA+ neurons were only observed within the hypothalami of the five species of bird studied, with no OxA+ neurons being observed in regions adjacent to the hypothalami (as sometimes observed for neurons of the orexinergic zona incerta cluster of mammals, e.g., Malungo et al, 2020;Oddes et al, 2023). Within the Hyp, the OxA+ neurons were located around the mid-rostrocaudal level of this structure (Figures 1-10).…”

“…In these two reptiles, orexinergic neurons were observed in the periventricular preoptic area, the dorsolateral hypothalamic nucleus, and the infundibulum. In the over 50 species of mammal studied, orexinergic neurons are typically found in three clusters, the main, zona incerta, and optic tract clusters; however, in microchiropteran bats, the optic tract cluster is absent, while additional clusters are observed in other species (Oddes et al., 2023).…”

“…This consistency indicates that the way the orexinergic system exerts its effect on the avian brain may be very similar across species, although detailed physiological studies would be needed to confirm this indicative anatomy. In comparison, studies in over 50 mammal species (Oddes et al, 2023) and 2 species of reptile (Domínguez et al, 2010) have revealed both consistencies and variances in the clustering of orexinergic neurons, indicating a potentially greater variability in orexinergic effects in the mammalian and reptilian brains when compared to the avian brain.…”

“…Some of the reported differences in the distribution and parcellation of orexinergic neurons in mammals appear to be associated with high volume diets, such as the presence of the parvocellular orexinergic cluster in the medial Hyp (Davimes et al, 2017;Dell et al, 2012;Dell, Karlsson, et al, 2016;Ettrup et al, 2010;Iqbal et al, 2001;Malungo et al, 2020;Maseko et al, 2013;Oddes et al, 2023), while others, such as the presence of orexinergic neurons in the ventral aspect of the medial supraoptic region of the Hyp (Oddes et al, 2023;Williams et al, 2022), have uncertain function. In addition, it should be noted that these variations in the parcellation of orexinergic neurons in mammals appear to be broadly associated with brain size, such that larger brained mammals appear to have more orexinergic clusters than smaller brain mammals; for example, smaller brained carnivores (compare ferret and nine-banded mongoose, Pillay et al, 2017, with African and Asian lion and cheetah, Oddes et al, 2023), and smaller brained primates (compare prosimians/macaque monkeys with apes, Williams et al, 2022;Oddes et al, 2023) have fewer distinct orexinergic clusters than the larger brained representatives within these lineages.…”

“…The orexinergic system plays a role in the regulation of wakefulness/sleep, specifically the maintenance of wakefulness (e.g., Inutsuka & Yamanaka, 2013; Volkhoff, 2012), and appetite, through the stimulation of food intake and the repression of neural circuits controlling satiety (e.g., Kukkonen et al., 2002; Soya & Sakurai, 2020; Zhang et al., 2013), making it a crucial regulatory link balancing the two biological imperatives of obtaining nutrition and sleep, both essential for survival. Orexinergic neurons are typically located within the hypothalamus (Hyp) in vertebrates (e.g., Domínguez et al., 2010; López et al., 2009; Matsuda et al., 2012; Singletary et al., 2006; Nixon & Smale, 2007; Fokidis et al., 2019; Miranda et al., 2013), but the majority of studies have focused upon mammals, with over 50 species having been studied (Oddes et al., 2023), and although there is general similarity in the distribution and nuclear parcellation of the orexinergic neurons in mammals, there are variances.…”