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The neuromolecular basis of adaptation to bond loss

适应键损失的神经分子基础

基本信息

批准号：
10374344
负责人：
Zoe Rebecca Donaldson
金额：
$ 60.38万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-07 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10374344
关键词：
Ablation Address Adult Age Aggressive behavior Animal Model Animals Atlases Behavior Behavioral Bereavement Biological Biological Process Brain Cells Data Disease Distress Emotional Exhibits Face Failure Future Gene Activation Gene Expression Gene Expression Profile Genetic Genetic Transcription Grief reaction Health Immediate-Early Genes Impaired health Impairment In Situ Hybridization Individual Intervention Investigation Life Maps Mediating Mental disorders Microtus Modeling Molecular Neurons Nucleus Accumbens Pain Pair Bond Partner in relationship Pathologic Pattern Persons Phenotype Physiological Play Population Process Proxy Psyche structure Risk Rodent Model Role Series Social Behavior Social isolation Spouses Study models Sum Testing Therapeutic Time biological adaptation to stress daily functioning diphtheria toxin fragment A experience experimental study improved insight loved ones novel pandemic disease prairie vole preference relating to nervous system response selective expression sex single-cell RNA sequencing social societal costs therapeutic target

项目摘要

Project Summary Loss of a loved one elevates the risk for physical and mental illness and leads to impaired daily function. For most people, the deleterious effects of loss improve with time. However, in a subset of bereaved individuals, the failure to adapt leads to pathological manifestations of loss and an extension of bereavement-associated health impairments. A lack of investigation into the neuronal and molecular processes that underlie healthy adaptation to loss has hampered our ability to ameliorate the negative consequences of loss. To address this gap in our understanding, we propose to use partner separation in monogamous prairie voles to operationally produce loss. Socially monogamous prairie voles form life-long pair bonds and exhibit distress upon partner separation. However, pairs bonds fade with time after partner separation, as evidenced by reduced bonding- related behaviors. To identify the key neural and molecular changes that underlie the adaptive processes engaged after loss of a partner, we will compare voles with intact partner bonds to those who have been separated from their partner. In Aim 1, we will comprehensively assess behavioral and transcriptional responses to partner separation over time. In Aim 2, we will ask how the molecular identity of the neurons responsive to partner interaction changes as a function of separation time. Finally, in Aim 3 we will test the hypothesis that ablation of partner-active neurons facilitates bond dissolution and enables the vole to form a new bond. Together, these experiments will provide the first insights into key neuromolecular changes that underlie adaptation to loss, thereby representing potential therapeutic targets for treating the negative aspects of grief and Prolonged Grief Disorder.

项目摘要失去亲人会增加身体和精神疾病的风险，并导致日常功能受损。为对大多数人来说，失去的有害影响会随着时间的推移而改善。然而，在一个丧失亲人的人的子集中，不能适应导致丧失的病理表现和与丧亲相关的健康的延伸损伤缺乏对构成健康基础的神经元和分子过程的研究对损失的适应阻碍了我们减轻损失的负面后果的能力。为了解决这个在我们的理解差距，我们建议使用伴侣分离在一夫一妻制的草原田鼠，产生损失。社会性一夫一妻制的草原田鼠形成终身的配偶关系，并对伴侣表现出痛苦分居然而，在伴侣分离后，随着时间的推移，伴侣间的结合会逐渐减弱，这一点可以从减少的结合中得到证明。相关行为。识别适应过程背后的关键神经和分子变化在失去伴侣后订婚，我们将比较伴侣关系完整的田鼠和那些在失去伴侣后订婚的田鼠。与伴侣分离。在目标1中，我们将全面评估行为和转录随着时间的推移，伴侣的分离。在目标2中，我们将问神经元的分子身份如何对作为分离时间的函数的伴侣互动变化作出响应。最后，在目标3中，我们将测试这一假说认为，消融伴侣活性神经元有助于债券溶解，并使田鼠形成一个新债券。总之，这些实验将提供对关键神经分子变化的第一次洞察，是对失去的适应的基础，因此代表了治疗消极方面的潜在治疗靶点。和长期悲伤障碍