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

社会动机的神经基础和无法适应损失

基本信息

批准号：
9933419
负责人：
Zoe Rebecca Donaldson
金额：
$ 15.66万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-05-31
项目状态：
已结题

项目摘要

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.

项目概要家庭成员和朋友之间的社会纽带可以持续一生。只要这些执着存在，驱使我们寻找这些人并与他们互动的选择性动机代表着一种健康的、强化的维持这些债券的机制。但是，当纽带被破坏时，这些激励系统会发生什么？永久丢失？大多数人最终都会学会适应失去亲人，但对某些人来说，无法适应适应会导致功能受损的悲伤，这种悲伤可能会持续数年。临床上，这被称为复杂性悲伤。尽管社会动机过程的核心重要性及其在失去后的适当转变，其神经元基础仍不清楚。为了解决这一缺陷，我建议使用一夫一妻制的草原田鼠，它们形成终生的纽带，并在与伴侣分离后表现出痛苦。成对的草原田鼠将撬开—— 迫切希望与他们的伴侣团聚，使我们能够量化债券导向的动机。我的实验室正在开发一个高通量操作系统来量化债券导向的动机。我将结合这种新颖的行为使用先进的神经发生工具来探究债券导向动机的神经元基础的范例。我将测试债券强度是否可以预测合作伙伴导向的动机水平以及这种动机的速度有多快伴侣永久分离后消失。然后，结合使用我们的操作范式体内 Ca2+ 成像和神经元活动的细胞特异性操作，我将检验以下假设：与奖励相关的大脑区域内的神经元群调节伙伴导向的动机。最后，因为有些人会经历病态的悲伤，其特征是持续沉迷于失去的联系，我会询问人为地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。完成这些实验将提供基本的见解在神经元水平上参与社会动机系统——无论是当纽带保持完整还是其破坏之后。这项研究的迫切需要；目前还没有公认的范式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，将会出现丧亲之痛引发的精神疾病、心脏病、和复杂的悲伤，这项工作代表了阐明重要生物机制的一种手段促成了这些现象。