Assessing the development of hippocampus-amygdala interactions during emotional l

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（尤其是学习、记忆和情感表达）最好被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周围，包括海马体、杏仁核和皮层的边缘相关区域。然而，这些系统的功能开发才刚刚开始被理解。根据所涉及的特定神经基质，即使是非常相似的学习、记忆和情绪处理任务似乎也有不同的个体发生特征。例如，已经确定的是，与离散线索形成厌恶联系的能力，如听觉或视觉经典恐惧条件反射所证明的，出现在与物理环境形成情感联系的能力之前，如情境恐惧条件反射所证明的。由于厌恶记忆都依赖于杏仁核，但空间记忆和情境记忆只依赖于海马体，这些发现被解释为海马体发育相对较慢。然而，我们实验室最近的数据对这个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）比以前认为的要早。在将这些类型的经历与情感事件结合起来以及对特定环境表达恐惧的能力之前，还需要进一步的发展。此外，对明确提示（依赖于杏仁核）表达恐惧的能力在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，数据显示，与之前的理解相反，海马体依赖记忆系统早在大鼠第17天就开始运作，而杏仁核依赖系统继续成熟。使用情境和暗示恐惧条件反射协议，当前的项目通过测试新的假设来检验杏仁核和海马体功能和相互作用的出现，即杏仁核-海马体的相互作用是导致发育迟缓的原因。为了验证这一假设，我们将从多方面考察行为操纵、即时早期基因表达和暂时药物失活对恐惧条件反射的影响。总的来说，这个项目将阐明在发育中的大鼠中控制使用物理环境来调节厌恶情绪表达的神经结构。

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.