Neuronal basis of social motivation and the failure to adapt to loss

项目摘要 家庭成员和朋友之间的社会纽带可以持续一生。只要这些附件存在， 驱使我们寻找这些人并与之互动的选择性动机代表着一种健康的、强化的 维持这些联系的机制。但是，当一种纽带被 永远迷失了？大多数人最终会学会适应失去所爱的人，但对一些人来说， 适应会导致功能受损的悲痛，可能会持续数年。在临床上，这被称为复杂的悲伤。尽管 社会激励过程的核心重要性及其在丧失后的适当转变，其 神经基础仍不清楚。为了解决这个缺陷，我建议使用一夫一妻制的草原田鼠，它形成了 终生结合，并在与伴侣分离后表现出痛苦。结对的草原田鼠将杠杆式- 按键与他们的合作伙伴团聚，使我们能够量化债券导向的动机。我的实验室正在研发一种 高通量操作系统，用于量化债券导向的动机。我将结合这本小说《行为》 用先进的神经遗传学工具来询问债券导向动机的神经元底物的范例。 我将测试纽带强度是否能预测合作伙伴导向的激励水平，以及这种激励有多快。 永久合作伙伴分离后终止。然后，使用我们的操作范式结合in 体内钙离子成像和细胞特异性操纵神经元的活动，我将检验这一假设 奖赏相关脑区的神经元群调节伴侣导向的动机。最后，因为 有些人会经历病态的悲痛，其特点是执着于失去的纽带，我会 问一问，人工重新激活编码成对键的神经元组合是否会导致延长 债券损失后的动机反应。这些实验的完成将提供基本的见解 在神经元水平上参与社会动机系统--无论是在纽带保持完整的情况下，还是在 在它被扰乱之后。迫切需要这项研究；目前还没有被接受的范例 研究选择性的社会动机或对损失的情绪反应。随着美国人口老龄化，将会有 丧亲导致的精神疾病、心脏病、 和复杂的悲痛，这项工作代表了一种手段，以阐明重要的生物机制， 造成了这些现象。

Project Summary Social bonds between family members and friends can last a lifetime. As long as these attachments exist, the selective motivation that drives us to seek out and interact with these individuals represents a healthy, reinforcing mechanism that maintains these bonds. But what happens to these motivational systems when a bond is permanently lost? Most people eventually learn to adapt to the loss of a loved one, but for some, the failure to adapt leads to function-impairing grief that can last years. Clinically, this is known as complicated grief. Despite the central importance of socio-motivational processes and their appropriate transformation following loss, their neuronal basis remains unclear. To address this deficit, I propose to use monogamous prairie voles, which form life-long bonds and exhibit distress following separation from their partner. Pair-bonded prairie voles will lever- press to be reunited with their partner, enabling us to quantify bond-directed motivation. My lab is developing a high-throughput operant system to quantify bond-directed motivation. I will combine this novel behavioral paradigm with advanced neurogenetic tools to interrogate the neuronal substrates of bond-directed motivation. I will test whether bond strength predicts levels of partner-directed motivation and how quickly this motivation extinguishes following permanent partner separation. Then, using our operant paradigm in combination with in vivo Ca2+ imaging and cell-specific manipulations of neuronal activity, I will test the hypothesis that distinct neuronal populations within reward-related brain regions modulate partner-directed motivation. Finally, because some people experience pathological forms of grief characterized by persistent dwelling on the lost bond, I will ask whether artificially reactivating the neuronal ensemble that encodes a pair bond leads to prolonged motivational responses following bond loss. Completion of these experiments will provide fundamental insights into the engagement of social motivation systems at a neuronal level – both when a bond remains intact and following its disruption. There is a pressing need for this research; there are no currently accepted paradigms for studying selective social motivation or the emotional response to loss. As the U.S. population ages, there will be a substantial public-health burden from increased rates of bereavement-induced mental illness, heart disease, and complicated grief, and this work represents a means to elucidate important biological mechanisms that contribute to these phenomena.