Dopaminergic plasticity underlying bonding and loss

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Project Summary: While strong and healthy social relationships positively contribute to our health and wellbeing, their loss is detrimental for our mental and physical health. Monogamous prairie voles (Microtus ochrogaster) provide an ideal species to examine the neurobiology of social bonding and loss. Prior work has shown that activation of dopamine (DA) receptors in the nucleus accumbens is a critical mediator of bond formation and maintenance. Specifically, DA receptor activation is essential for forming selective affiliation towards a mating partner and subsequent aggression towards non-partners, suggesting that the functional role of DA in the nucleus accumbens transitions from partner affiliation to non-partner aggression as the bond matures. Other work suggests plasticity of the accumbal DA system accompanies bonding, including changes in DA receptor expression and ex vivo DA release. However, changes in receptor expression or capacity for release do not fully explain the shift in the function of DA from partner affiliation to novel aggression. DA release and activation of receptors needs to be context specific in order to display the appropriate behavior towards the partner or novel voles. Thus, my research examines how the dopaminergic system changes as a function of bonding in loss, including changes in release between the partner and novel voles. To do so, my dissertation leverages GRABDA and fiber photometry, two tools that I developed in prairie voles, to detect in vivo DA release in behaving voles with millisecond resolution. I use these tools to investigate three ways in which social bonding and loss can cause plasticity in the DA system that mediates the transition in bonding behaviors. In Aim 1 I ask whether there are bonding induced in vivo changes in DA release capacity. My preliminary work shows that initial bond formation and bond loss decreases optogenetically evoked DA release in the nucleus accumbens. Aim 1 will determine whether my observed results are specifically due to bonding/loss from an opposite sex partner, not from other experimental conditions or general social isolation. In Aim 2, I examine how DA release elicited by unrestricted social interaction with a partner or novel vole changes during bond maturation and loss. Finally, in Aim 3, I use a social operant paradigm to distinguish DA release during the appetitive and consummatory aspects of interaction with a partner or novel across bonding and loss. In sum, this proposal uses novel behavioral and technical approaches in prairie voles to provide insights into the dopaminergic dynamics that contribute to within- individual plasticity that enables social bonding.