The neuromolecular basis of adaptation to bond loss

适应键损失的神经分子基础

• 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
• 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

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 失去亲人会提高身体和精神疾病的风险，并导致每日功能受损。为了 大多数人，损失的有害影响会随着时间的推移而改善。但是，在一个失去亲人的个体的子集中 无法适应会导致损失的病理表现和丧亲相关的健康的扩展 障碍。缺乏对健康基础的神经元和分子过程的研究 适应损失已阻碍我们改善损失的负面后果的能力。解决这个问题 在我们的理解中，我们建议使用一夫一妻制的伴侣分离到运营 产生损失。社会一夫一妻制的草原田鼠形成终身二人的纽带，并对伴侣表现出困扰 分离。然而，伴侣分离后的时间对键逐渐淡出，这是通过降低的键合所证明的。 相关行为。确定自适应过程构成的关键神经和分子变化 失去伴侣后，我们将与曾经的伴侣债券进行比较 与他们的伴侣分开。在AIM 1中，我们将全面评估行为和转录 随着时间的流逝，对伴侣分离的响应。在AIM 2中，我们将询问神经元的分子身份如何 响应伴侣的交互作用随着分离时间而变化。最后，在AIM 3中，我们将测试 伴侣活性神经元消融的假设有助于键溶解，并使Vole形成A 新债券。这些实验将共同提供对关键神经分子变化的首次见解 对损失的适应基础，从而代表了治疗负面方面的潜在治疗靶标 悲伤和长期的悲伤障碍。