Oxytocin receptors are widely distributed in prairie vole (Microtus ochrogaster) brain: relation to social behavior, genetic polymorphisms, and the dopamine system

• Type of Material: Article
• Authors: Kiyoshi Inoue, Emory University; Charles L. Ford, Emory University; Kengo Horie, Emory University; Larry Young, Emory University
• Language: English
• Date: 2022-06-28
• Publisher: John Wiley and Sons
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Wiley Periodicals LLC.
• Final Published Version (URL): https://doi.org/10.1002/cne.25382
• Title of Journal or Parent Work: Journal of Comparative Neurology
• Volume: 530
• Issue: 16
• Start Page: 2881
• End Page: 2900
• Grant/Funding Information: This work was supported by NIH grants R01MH112788 and P50MH100023 to LJY, and P51OD11132 to Emory National Primate Research Center
• Keywords: phenotypic plasticity; nucleus accumbens; in situ hybridization; dopamine receptor; Oxtr mRNA; Oxtr SNPs; autoradiography
• Research Categories: Biology, Neuroscience

Abstract

Oxytocin regulates social behavior via direct modulation of neurons, regulation of neural network activity, and interaction with other neurotransmitter systems. The behavioral effects of oxytocin signaling are determined by the species-specific distribution of brain oxytocin receptors. The socially monogamous prairie vole has been a useful model organism for elucidating the role of oxytocin in social behaviors, including pair bonding, response to social loss, and consoling. However, there has been no comprehensive mapping of oxytocin receptor-expressing cells throughout the prairie vole brain. Here, we employed a highly sensitive in situ hybridization, RNAscope, to construct an exhaustive, brain-wide map of oxytocin receptor mRNA-expressing cells. We found that oxytocin receptor mRNA expression was widespread and diffuse throughout the brain, with specific areas displaying particularly robust expression. Comparing receptor binding with mRNA revealed that regions of the hippocampus and substantia nigra contained oxytocin receptor protein but lacked mRNA, indicating that oxytocin receptors can be transported to distal neuronal processes, consistent with presynaptic oxytocin receptor functions. In the nucleus accumbens, a region involved in oxytocin-dependent social bonding, oxytocin receptor mRNA expression was detected in both the D1 and D2 dopamine receptor-expressing subtypes of cells. Furthermore, natural genetic polymorphisms robustly influenced oxytocin receptor expression in both D1 and D2 receptor cell types in the nucleus accumbens. Collectively, our findings further elucidate the extent to which oxytocin signaling is capable of influencing brain-wide neural activity, responses to social stimuli, and social behavior.