Oxytocin‐ and arginine vasopressin‐containing fibers in the cortex of humans, chimpanzees, and rhesus macaques

Abstract

Oxytocin (OT) and arginine-vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non-human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT- and AVP-producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself. However, OT and AVP also influence social cognition, including effects on social recognition, cooperation, communication, and in-group altruism, which suggests connectivity with cortical structures. While OT and AVP V1a receptors have been demonstrated in the cortex of rodents and primates, and intranasal administration of OT and AVP has been shown to modulate cortical activity, there is to date little evidence that OT-and AVP-containing neurons project into the cortex. Here, we demonstrate the existence of OT- and AVP-containing fibers in cortical regions relevant to social cognition using immunohistochemistry in humans, chimpanzees, and rhesus macaques. OT-immunoreactive fibers were found in the straight gyrus of the orbitofrontal cortex as well as the anterior cingulate gyrus in human and chimpanzee brains, while no OT-immunoreactive fibers were found in macaque cortex. AVP-immunoreactive fibers were observed in the anterior cingulate gyrus in all species, as well as in the insular cortex in humans, and in a more restricted distribution in chimpanzees. This is the first report of OT and AVP fibers in the cortex in human and non-human primates. Our findings provide a potential mechanism by which OT and AVP might exert effects on brain regions far from their production site in the hypothalamus, as well as potential species differences in the behavioral functions of these target regions.

AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees

“…In contrast, the DupB+/− chimpanzees show lesser gray matter covariation than DupB−/− chimpanzees in regions comprising component 6, including the superior temporal sulcus and the postcentral sulcus. These regional differences overlap with brain regions previously found to differ in vasopressin and oxytocin neural fibers between nonhuman primates, and in AVPR1A gene expression in humans with different RS3 alleles (cingulate, insula and the hippocampus) . Moreover, several of the larger regions identified in components 4‐6 overlap with those that comprise the social brain network (prefrontal cortex, insula, cingulate and superior temporal sulcus), which is consistent with our hypothesis that these polymorphisms affect brain structures inolved in regulation of social cognition and behavior.…”

“…In humans, variation in RS3 is related to activation of the amygdala during a face recognition task, an observation that supports the amygdala theory of autism . Immunohistochemistry analyses have revealed species similarities and differences in both oxytocin and vasopressin fibers in regions of the human, chimpanzee and rhesus macaque cortex . With respect to vasopressin, fibers were found in the anterior olfactory nucleus, primary olfactory cortex and subgenual region of the anterior cingulate cortex of all three species.…”

“…With respect to vasopressin, fibers were found in the anterior olfactory nucleus, primary olfactory cortex and subgenual region of the anterior cingulate cortex of all three species. However, vasopressin fibers were present in the agranular insula cortex and orbitofrontal cortex of humans and chimpanzees, but were absent in rhesus monkeys, and were found in the dysgranular insula and frontal operculum in humans only . Species differences have also been found in AVPR1A expression, with receptor binding in the amygdala, stria terminalis, lateral septum, hypothalamus and brainstem of rhesus macaques (similar to rodents), but spread throughout the cortex of titi monkeys (particularly in the insula, cingulate and occipital cortex) …”

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction

“…In this area, its anxiolytic activity is brought about by the recruitment of an oxytocin receptor (OTR)-TRPV2 channels (and subsequent Ca2+ influx)-MEK1/2 pathway (van den Burg et al 2015). Underlying mechanisms of oxytocin and fear extinction in other brain regions, like the PFC and amygdala, are beginning to be explored, motivated by the discovery of OT release and OTR expression in those areas (Knobloch et al 2012;Mitre et al 2016;Li et al 2016;Rogers et al 2018).…”

Musculoskeletal Pain and Brain Morphology: Oxytocin’s Potential as a Treatment for Chronic Pain in Aging

“…While there are some key differences, there is also overlap in OXTR expression concentrations in the CNS across species (Insel, 2010), including non-human primates (Freeman and Young, 2016). Rogers et al (2018), for example, found OT immunoreactive fibers in the straight gyrus of the orbitofrontal cortex and anterior cingulate gyrus, a region involved in pain processing, in both humans and chimpanzees, but not macaques. Immunohistological investigation of the ventral hypothalamus of the macaque showed the presence of OXTR in the septal nucleus and preoptic area (Boccia et al, 2001).…”