The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

Abstract

The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication.

Neural mechanisms of social decision-making in the primate amygdala

“…Inhaled OT increases OT concentration in the central nervous system and enhances both prosocial preferences and social attention in rhesus macaques (33). Recently, it has been demonstrated that OT administration modulates hemodynamic activity in the amygdala in rhesus macaques (30), and it has been hypothesized that the primate amygdala may express presynaptic OT receptors (46). If reward value-mirroring by the amygdala is critical for prosocial behavior, we reasoned that directly increasing OT levels in the amygdala would increase the likelihood that monkeys would make prosocial decisions.…”

Adaptations for social cognition in the primate brain

“…Lack of OT receptors in these classic reward circuits may underlie lack of pair-bond formation in polygynous meadow voles (Microtus pennsylvanicus) and montane voles (Microtus montanus) [122]. Recent studies have demonstrated that OT receptors in both monogamous titi monkeys (Callicebus cupreus) and rhesus macaques [127,128] appear to be limited to areas of the hypothalamus and brainstem implicated in arousal and visual orienting behaviour. Notably, vasopressin receptors are much more widespread in cortex and basal ganglia, and OT may bind to these receptors when released at higher volumes or delivered exogenously.…”

Oxytocin modulates fMRI responses to facial expression in macaques

“…In the rhesus monkey brain, OT receptors are most robustly expressed in the nucleus basalis of Meynert, the superficial gray layer of the superior colliculus, the pedunculopontine tegmental nucleus, the trapezoid body, and the ventromedial hypothalamus (37). Although (a high density of) OT receptors have not been found in the selected ROIs of the present study, including the amygdala, activity in these ROIs may be modulated by projections from areas that contain OT receptors, and thereby influence social behavior and cognition.…”