The neuromolecular basis of adaptation to bond loss

项目摘要 失去所爱的人会增加身体和精神疾病的风险，并导致日常功能受损。为 对于大多数人来说，损失的有害影响会随着时间的推移而改善。然而，在一群失去亲人的人中， 不适应会导致丧失的病理表现和与丧亲相关的健康的延长 减损。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改善损失的负面后果的能力。要解决这个问题 在认识上的差距，我们建议在一夫一妻制的草原田鼠中使用伴侣分离来操作 产生损失。社会上一夫一妻制的草原田鼠形成了终生的伴侣纽带，并对伴侣表现出痛苦 分离。然而，在伴侣分离后，伴侣之间的结合会随着时间的推移而褪色，这一点从结合的减少中可见一斑。 相关行为。确定适应过程背后的关键神经和分子变化 在失去伴侣后，我们将比较伙伴关系完好无损的田鼠和那些已经 和他们的伴侣分开了。在目标1中，我们将全面评估行为和转录 随着时间的推移，对合作伙伴离职的反应。在目标2中，我们将询问神经元的分子同一性是如何 对作为分离时间函数的合作伙伴交互变化作出响应。最后，在目标3中，我们将测试 假设消融伙伴激活的神经元有助于键的溶解，并使田鼠能够形成 新的纽带。总之，这些实验将提供对关键神经分子变化的首次洞察，这些变化 潜在的对丧失的适应，从而代表了治疗负面方面的潜在治疗靶点 悲痛和长期的悲痛障碍。

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.