Oxytocin receptor neurons in the anterior cingulate cortex regulate consoling in monogamous prairie voles (Microtus ochrogaster) Restricted; Files & ToC

Abstract

Empathy describes the process of recognizing and relating to the emotional states of others and is critical for communication and cohesion among groups of individuals. Deficits in empathy are characteristic of several psychiatric conditions; however, the neurobiological mechanisms underlying empathy are not well characterized. Consolation, or comforting contact directed toward a distressed party, is an empathy-like response observed across species including in monogamous prairie voles (microtus orchogaster). Consolation induces neural activity in the anterior cingulate cortex (ACC) of prairie voles and this region is also implicated in empathy in humans, suggesting conserved neural substrates of empathy across species. The work in this dissertation aimed to further characterize the neuromdoulatory mechanisms driving ACC involvement in prairie vole consoling. We first chemogenetically inhibited ACC activity in adult prairie voles during a task designed to elicit consoling responses, finding that consoling responses were maintained. Next, we specifically inhibited neurons in the ACC expressing the gene for the oxytocin receptor (Oxtr). Oxytocin (OT) is a neuropeptide hormone that binds to OXTRs and regulates a variety of social behaviors, such as empathy-like responses. Selective targeting of Oxtr-expressing cells was accomplished by using transgenic Oxtr-P2A-cre prairie voles, newly developed by our group. Inhibition of ACC^Oxtr neurons blunts consoling but increases sniffing, suggesting that OT modulates neurons that may regulate both prosocial comforting and investigative behaviors in opposing directions. We next used CRISPR/ Cas9 to genetically delete OXTRs in the ACC, resulting in disrupted consoling, but no changes to sniffing or other behaviors. OT, via it’s receptor, modulates the activity of cells in the ACC that regulate consoling responses in prairie voles towards their partner. Oxtr expresses primarily in excitatory ACC neurons and ACC^Oxtr neurons account for a substantial proportion of ACC inputs to the nucleus accumbens (NAc). These findings illuminate a circuit modulated by OT that may promote consoling responses. Finally, we found evidence of consoling toward strangers in socially isolated mice and find that reward preferences are altered by pairing rewards with exposure to a distressed, compared to a neutral, animal. The work in this dissertation constitutes some of the first behavioral manipulations using Oxtr-P2A-cre prairie voles and expands our understanding of OT signaling within the ACC.

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Neuroscience
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Neuroscience
Palabra Clave	prairie vole oxytocin empathy-like behavior anterior cingulate cortex
Committee Chair / Thesis Advisor	Shannon Gourley, Emory University Zachary Johnson, Emory University
Committee Members	Malavika Murugan, Emory University Yoland Smith, Emory University John Christianson, Boston College

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