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.

项目摘要家人和朋友之间的社会纽带可以持续一生。只要存在这些附件，选择性动机驱使我们寻求和与这些人互动代表健康，增强维持这些纽带的机制。但是，当纽带是什么时候会发生什么永久失去？大多数人有时会学会适应失去亲人的失落，但是对于某些人来说，适应可能会持续数年的功能障碍。临床上，这被称为复杂的贪婪。尽管社会动机过程的核心重要性及其在损失后的适当转变，他们神经元基础尚不清楚。为了解决这种辩护，我建议使用一夫一妻制的草原田鼠与伴侣分开后，终身纽带和暴露困扰。配对的大草原田鼠将杠杆按下要与他们的伴侣团聚，使我们能够量化债券指导的动机。我的实验室正在开发一个高通量操作系统以量化键指导的动机。我将结合这种新颖的行为具有先进的神经遗传学工具的范式询问键指导动机的神经元基质。我将测试债券强度预测合作伙伴指导的动机的水平以及这种动机的速度在永久合作伙伴分离之后熄灭。然后，将我们的操作员范式与IN结合使用体内Ca2+成像和神经活性的细胞特异性操纵，我将测试以下假设与奖励相关的大脑区域内的神经元种群调节伴侣指导的动机。最后，因为有些人体验了贪婪的病理形式，其特征是持续居住在失去的纽带上，我会询问编码一对键的神经元合奏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 - 当债券保持完整时，遵循其中断。这项研究迫切需要；目前没有接受的范例研究选择性的社会动机或对损失的情感反应。随着美国人口的年龄，将会有丧亲引起的精神疾病，心脏病，和复杂的悲伤，这项工作代表了阐明重要生物学机制的意义有助于这些现象。