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了一种健康的、强化的 保持这些联系的机制。但是当一种联系被 永远失去？大多数人最终学会适应失去亲人，但对一些人来说， 适应会导致功能受损的悲伤，这种悲伤可能持续数年。临床上，这被称为复杂性悲伤。尽管 社会动机过程及其在损失后的适当转变的核心重要性， 神经元基础尚不清楚。为了解决这个问题，我建议使用一夫一妻制的草原田鼠， 终身结合，并在与伴侣分离后表现出痛苦。配对的草原田鼠会撬起- 与伴侣团聚的压力，使我们能够量化债券导向的动机。我的实验室正在开发一种 高通量操作系统，以量化债券导向的动机。我会将联合收割机这种新颖的行为 范式与先进的神经遗传学工具，询问神经基板的债券导向的动机。 我将测试是否债券强度预测水平的合作伙伴为导向的动机和如何迅速这种动机 在永久伴侣分居后离婚。然后，使用我们的操作范式结合在 体内Ca 2+成像和神经元活动的细胞特异性操作，我将测试不同的假设， 奖赏相关脑区的神经元群体调节伴侣导向的动机。最后因为 有些人经历了病理性的悲伤，其特征是持续地沉浸在失去的联系中，我会 问人工重新激活编码配对键的神经元集合是否会导致延长 失去联系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-无论是当债券保持完整， 在其中断之后。这项研究是迫切需要的;目前还没有公认的范式， 研究选择性社会动机或对损失的情绪反应。随着美国人口老龄化， 由于丧亲引起的精神疾病、心脏病、 和复杂的悲伤，这项工作代表了一种手段来阐明重要的生物机制， 促成了这些现象。

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.