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）：越来越同意，最好将许多复杂的认知功能（尤其是学习，记忆和情感表达）理解为需要半独立的神经回路之间的相互作用，这些神经回路集中在各种边缘系统结构上，包括海马，amygdala，amygdala和limbic corpied corortex的层。但是，这些系统的功能开发才开始被理解。根据所涉及的特定神经底物，即使学习，记忆和情感处理任务也似乎具有不同的个体发育特征。例如，已经有充分的确定是，在听觉或视觉经典恐惧条件上证明，在与身体环境形成情感联系之前，出现了与离散线索形成厌恶性关联的能力，如上下文恐惧条件所证明。由于厌恶记忆都取决于杏仁核，但是空间和上下文记忆独特地取决于海马，因此这种发现被解释为表明海马相对较慢的发展。但是，我们实验室的最新数据提出了这一想法的两个挑战。首先，比以前认为的早期表现形成环境的表示能力（取决于海马）。在能够将这些类型的经验与情感事件结合并向特定环境表达恐惧的能力之前，需要进一步发展。此外，表达恐惧的能力（取决于杏仁核）在最初出现后的一段时间内持续一段时间，比以前认为的要长。因此，数据表明，与先前的理解相反，海马依赖性记忆系统早在大鼠的第17天就起作用，并且依赖杏仁核的系统继续成熟。当前项目使用上下文和提示的恐惧条件方案，研究了杏仁核和海马功能的出现以及通过测试新的假设，即它慢速开发了杏仁核 - 海马 - 海马相互作用，这些相互作用负责发育延迟。为了检验这一假设，将在各个方面检查恐惧条件的各个方面，将检查行为操纵，立即的基因表达和临时药理失活的影响。总体而言，该项目将阐明使用物理环境来调节发育中的厌恶情绪表达的神经结构。 公共卫生相关性：该项目研究了边缘系统功能的发展。重点是创建和检查一个范式，该范式可用于评估包括海马和杏仁核在内的主要边缘系统结构之间的连通性。尽管对于它们在完整发展的生物体中的功能相互作用方面，知之甚少，但这些结构之间的连通性似乎在几种发育障碍中发生了改变，包括主要的精神病，自闭症和焦虑症。因此，除了促进我们对典型发展的理解外，这些实验还将为将来的研究打开大门，以进一步阐明这些疾病的机制。因此，该项目将提供数据，从而更好地理解边缘系统的开发以及创建更好的发育障碍动物模型。