Identifying a role for the amygdala in social behavior deficits following early-life trauma

确定杏仁核在早期创伤后社会行为缺陷中的作用

• 批准号: 9402818
• 负责人: Maya Opendak
• 金额: $ 0.24万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402818
• 关键词: Address; Adult; Adverse effects; Age; Amygdaloid structure; Animal Model; Animals; Anxiety; Autistic Disorder; Behavior; Behavioral; Caregivers; Caring; Cell Nucleus; Child Abuse; Childhood; Complex; Data; Development; Disease; Early-life trauma; Ensure; Environment; Eye; FOS gene; Functional disorder; Growth; Health Services Accessibility; Human; Immediate-Early Genes; Impairment; Infant; Intervention; Knowledge; Life; Life Experience; Link; Literature; Longevity; Measures; Mediator of activation protein; Mental disorders; Modeling; Mothers; Partner in relationship; Pathway interactions; Prevalence; Rattus; Reproduction; Research; Resources; Rodent Model; Role; Safety; Severities; Social Behavior; System; Techniques; Telemetry; Testing; Trauma; Weaning; Wireless Technology; Work; anxiety-like behavior; course development; depressive symptoms; environmental enrichment for laboratory animals; experience; food protection; infancy; maltreatment; neglect; neural circuit; neurobehavioral; nonhuman primate; optogenetics; peer; postnatal; prevent; programs; pup; repaired; social; tool

Modified Project Summary/Abstract Section For many species, access to crucial resources, such as food, protection, and receptive mates, requires a highly coordinated and adaptable system of social behavior. Although the sensitivity of social behavior to previous experience can be adaptive, it also can be detrimental: research has shown that early-life experience, particularly trauma associated with a caregiver, has a unique ability to program social deficits that last well into adulthood. Data from a variety of species appears to converge on the amygdala as a central mediator of these impairments in social behavior. However, the specific role of the amygdala in producing social deficits following abuse, or whether this changes over the course of development, remain unclear. To address this gap in knowledge, and with an eye toward developing interventions, we propose to study social behavior and functional amygdala circuitry in a rodent model of early life abuse. Data from our lab and pilot data collected for this proposal supports the hypothesis that caregiver abuse produces persistent social deficits that emerge at weaning associated with dysregulation of amygdala circuitry, and that a period of environmental enrichment following abuse can prevent the emergence of impairments. Furthermore, the literature suggests a specific role for the basolateral (BLA) and central (CeA) amygdala nuclei in modulating social behavior. To test this, we have measured amygdala activation in rats that were reared in either typical (control) or abusive conditions during tests of social behavior at weaning and adulthood. Next, we will explore the efficacy of environmental enrichment on reversing the effects of early life abuse. Finally, we will dissect the amygdala circuitry causally involved in these effects using optogenetic tools. We have collected data showing that following abuse from a caregiver, peer social behavior deficits will emerge by weaning (PN23), persist into adulthood (PN60) and are linked to changes in BLA function. We hypothesize that 1) enrichment after abuse, but before emergence of neurobehavioral deficits induced by early-life abuse will restore typical social behavior and amygdala function, and 2) targeted optogenetic inhibition of the BLA-CeA circuit will normalize social behavior in abused animals to control levels. The work proposed here will begin to address the causal role of amygdala circuitry in producing social deficits following abuse and identify interventions to prevent emergence of neurobehavioral deficits following trauma.

修改后的项目摘要/摘要部分 对于许多物种来说，获得食物、保护和接受性伴侣等重要资源需要高度协调和适应性强的社会行为系统。尽管社会行为对先前经历的敏感性可以是适应性的，但它也可能是有害的：研究表明，早年经历，特别是与照顾者相关的创伤，具有独特的能力来规划持续到成年期的社会缺陷。 来自各种物种的数据似乎都集中在杏仁核上，认为杏仁核是这些社会行为障碍的中心调节者。 然而，杏仁核在虐待后产生社会缺陷中的具体作用，或者这种情况是否会在发育过程中发生变化，仍不清楚。 为了解决这一知识差距，并着眼于制定干预措施，我们建议研究早期生活虐待啮齿动物模型中的社会行为和功能性杏仁核回路。我们实验室的数据和为本提案收集的试点数据支持这样的假设：看护者虐待会产生持续的社会缺陷，这种缺陷在断奶时出现，与杏仁核回路失调相关，而虐待后一段时期的环境丰富可以防止损伤的出现。此外，文献表明基底外侧（BLA）和中央（CeA）杏仁核在调节社会行为中具有特定作用。为了测试这一点，我们在断奶和成年期的社会行为测试中测量了在典型（对照）或虐待条件下饲养的大鼠的杏仁核激活情况。接下来，我们将探讨环境丰富对于扭转早期生活虐待影响的功效。最后，我们将使用光遗传学工具剖析与这些效应相关的杏仁核回路。我们收集的数据显示，在受到看护者虐待后，同伴社交行为缺陷将在断奶时出现（PN23），并持续到成年期（PN60），并且与 BLA 功能的变化有关。我们假设：1）虐待后、早期虐待引起的神经行为缺陷出现之前的富集将恢复典型的社会行为和杏仁核功能，2）BLA-CeA 回路的靶向光遗传学抑制将使受虐待动物的社会行为正常化至控制水平。 这里提出的工作将开始解决杏仁核回路在虐待后产生社会缺陷中的因果作用，并确定预防创伤后神经行为缺陷出现的干预措施。