Dopaminergic plasticity underlying bonding and loss

项目总结： 虽然牢固和健康的社会关系对我们的健康和福祉有积极的贡献，但它们的损失是 对我们的身心健康有害。一夫一妻制的草原田鼠(Microtus Ochrogaster)提供了 是研究社会联系和丧失的神经生物学的理想物种。先前的研究已经表明，激活 伏核中的多巴胺(DA)受体是形成和维持键的关键介质。 具体地说，DA受体的激活对于形成对交配伙伴的选择性联系是必不可少的，并且 随后对非伙伴的攻击，表明多巴胺在核内的功能作用 随着债券到期，Vavbens从合伙人从属关系过渡到非合伙人攻击性。其他工作 提示伏隔区DA系统的可塑性伴随着结合，包括DA受体的变化 表达和体外释放DA。然而，受体表达或释放能力的变化不会 充分解释DA的功能从伙伴从属关系转变为新的攻击性。DA版本和 受体的激活需要是特定于上下文的，以便显示对 伴侣或新奇的田鼠。因此，我的研究考察了多巴胺能系统如何随着 损失中的结合，包括伴侣和新的田鼠之间释放的变化。 为了做到这一点，我的论文利用了GRABDA和纤维光度学，这两个工具是我在Prairie开发的 以毫秒的分辨率检测行为正常的田鼠体内DA的释放。我用这些工具来调查 社会联系和丧失可能导致DA系统中的可塑性的三种方式，而DA系统调节着这种转变 在粘合行为中。在目标1中，我询问体内是否存在结合诱导的DA释放的变化 容量。我的初步工作表明，初始成键和成键损失以光遗传的方式减少 在伏隔核诱发DA释放。目标1将决定我观察到的结果是否 特别是由于异性伴侣的结合/丧失，而不是由于其他实验条件或 普遍的社会孤立。在目标2中，我研究了不受限制的社交互动如何引发DA释放 伴侣或新的田鼠在债券到期和丢失期间发生变化。最后，在《目标3》中，我使用了一种社会行为方式 区分与人的胃口和食欲相互作用期间DA释放的范式 伴侣或小说，跨越结缘和失落。总而言之，这项提议使用了新颖的行为和技术 草原田鼠的方法提供了对多巴胺能动力学的洞察，这些动力学有助于- 个体的可塑性使社会联系在一起。

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.