Assessing the development of hippocampus-amygdala interactions during emotional l

评估情绪过程中海马-杏仁核相互作用的发展

• 批准号: 8232269
• 负责人: Michael A Burman
• 金额: $ 40.49万
• 依托单位: UNIVERSITY OF NEW ENGLAND
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8232269
• 关键词: Accounting; Adult; Age; Agreement; Amygdaloid structure; Animal Model; Anxiety; Anxiety Disorders; Auditory; Autistic Disorder; Behavior Control; Behavioral; Belief; Complex; Cues; Data; Development; Developmental Delay Disorders; Disease; Dorsal; Emotional; Emotions; Environment; Event; Fostering; Freezing; Fright; Future; Gene Expression; Growth; Hippocampus (Brain); Immediate-Early Genes; Learning; Limbic System; Mediating; Memory; Methods; Neurologic; Organism; Pattern; Physical environment; Procedures; Process; Protocols documentation; Psychotic Disorders; Rattus; Regulation; Research; Sensory; Signal Transduction; Staging; Structure; System; Systems Development; Testing; Time; Visual; cognitive function; conditioned fear; developmental disease; experience; innovation; mature animal; neural circuit; novel; postnatal; relating to nervous system; research study; showing emotion; theories; tool

DESCRIPTION (provided by applicant): There is growing agreement that many complex cognitive functions (especially learning, memory, and emotional expression) are best understood as requiring an interaction among semi-independent neural circuits focused around a variety of limbic system structures, including the hippocampus, amygdala and limbic-associated regions of cortex. However, the functional development of these systems is only beginning to be understood. Depending on the specific neural substrates involved, even very similar learning, memory and emotional processing tasks appear to have different ontogenetic profiles. For example, it has been well established that the ability to form aversive associations with discrete cues, as demonstrated by auditory or visual classical fear conditioning, emerges prior to the ability to form emotional associations with physical environments, as demonstrated by contextual fear conditioning. Since aversive memories all depend upon the amygdala, but spatial and contextual memories uniquely depend on the hippocampus, such findings had been interpreted as suggesting that the hippocampus was relatively slow to develop. However, recent data from our lab presents two challenges to this idea. First, the ability to form a representation of the environment (dependent upon the hippocampus) is present early than previously believed. Further development is required prior to the ability to integrate these types of experiences with emotional events and to express fear to a particular environment. Moreover, the ability to express fear to an explicit cue (dependent on the amygdala) continues to increase for some time after its initial emergence, longer than previously believed. Thus, the data show that contrary to previous understanding, the hippocampus-dependent memory system is functional as early as day 17 in rats, and the amygdala-dependent system continues to mature. Using contextual and cued fear conditioning protocols, the current project examines the emergence of amygdala and hippocampus functionality and interactions by testing the novel hypothesis that it is slow-developing amygdala- hippocampus interactions that are responsible for the developmental delay. To test this hypothesis, the effects of behavioral manipulations, immediate-early gene expression, and temporary pharmacological inactivation will be examined on various aspects fear conditioning. Overall this project will elucidate the neural structures governing the use of physical environments to regulate aversive emotional expression in developing rats. PUBLIC HEALTH RELEVANCE: This project investigates the development of limbic system function. The focus is to create and examine a paradigm that can be used to assess the connectivity between major limbic system structures including the hippocampus and amygdala. Although relatively little is known about how they functionally interact in intact developing organisms, the connectivity between these structures appears to be altered in several developmental disorders including major psychoses, autism and anxiety disorders. Thus, in addition to advancing our understanding of typical development, these experiments will open the door for future studies that further elucidate the mechanisms underlying these disorders. Therefore, this project will provide data leading to a better understanding of limbic system development and the creation of better animal models of developmental disorders.

描述（由申请人提供）：越来越多的人认为，许多复杂的认知功能（特别是学习、记忆和情绪表达）最好被理解为需要围绕各种边缘系统结构的半独立神经回路之间的相互作用，包括边缘系统结构。海马体、杏仁核和皮质边缘相关区域。然而，这些系统的功能开发才刚刚开始被了解。根据所涉及的特定神经基质，即使非常相似的学习、记忆和情感处理任务似乎也具有不同的个体发育特征。例如，众所周知，与离散线索形成厌恶关联的能力（如听觉或视觉经典恐惧条件反射所证明的那样）先于与物理环境形成情感关联的能力（如情境恐惧条件反射所证明的那样）出现。由于厌恶记忆都依赖于杏仁核，但空间和情境记忆独特地依赖于海马体，因此这些发现被解释为表明海马体的发育相对缓慢。然而，我们实验室的最新数据对这一想法提出了两个挑战。首先，形成环境表征的能力（取决于海马体）比之前认为的更早出现。在将这些类型的体验与情感事件结合起来并对特定环境表达恐惧的能力之前，需要进一步的发展。此外，对明确提示（取决于杏仁核）表达恐惧的能力在其最初出现后的一段时间内继续增强，比之前认为的要长。因此，数据表明，与之前的理解相反，大鼠的海马依赖性记忆系统早在第17天就发挥了功能，并且杏仁核依赖性系统继续成熟。当前的项目使用情境和暗示的恐惧调节方案，通过测试新的假设来检查杏仁核和海马体功能和相互作用的出现，即缓慢发展的杏仁核-海马体相互作用是导致发育迟缓的原因。为了检验这一假设，将在恐惧条件反射的各个方面检查行为操纵、早期基因表达和暂时药理学失活的影响。总体而言，该项目将阐明控制发育中老鼠使用物理环境来调节厌恶情绪表达的神经结构。 公共卫生相关性：该项目研究边缘系统功能的发展。重点是创建和检查可用于评估主要边缘系统结构（包括海马体和杏仁核）之间的连接性的范例。尽管人们对它们在完整的发育生物体中如何功能相互作用知之甚少，但这些结构之间的连接似乎在几种发育障碍中发生了改变，包括严重的精神病、自闭症和焦虑症。因此，除了增进我们对典型发育的理解之外，这些实验还将为未来的研究打开大门，进一步阐明这些疾病背后的机制。因此，该项目将提供数据，帮助更好地了解边缘系统发育并创建更好的发育障碍动物模型。