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Prefrontal interactions with hippocampus and amygdala during trace fear

微量恐惧期间前额叶与海马体和杏仁核的相互作用

基本信息

批准号：
8035493
负责人：
FRED J HELMSTETTER
金额：
$ 7.18万
依托单位：
UNIVERSITY OF WISCONSIN MILWAUKEE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8035493
关键词：
Address Affect Alzheimer&apos s Disease Amygdaloid structure Anatomy Area Attention deficit hyperactivity disorder Auditory Behavior Behavioral Paradigm Brain Brain region CREB1 gene Cell physiology Cognition Cognitive Cyclic AMP-Responsive DNA-Binding Protein Data Decision Making Disease Elements Episodic memory Event Fright Functional disorder Hippocampus (Brain)Human Investigation Laboratory Rat Learning MAP Kinase Gene Medial Memory Modality Modeling Molecular Molecular Neurobiology Monkeys Neurobiology Neuronal Plasticity Neurons Outcome Pattern Physiology Play Post-Traumatic Stress Disorders Prefrontal Cortex Process Protein Biosynthesis Rattus Relative (related person)Research Retrieval Role Schizophrenia Sensory Shock Short-Term Memory Signal Pathway Signal Transduction Site Structure Temporal Lobe Testing Time Training Work cognitive function conditioned fear conditioning foot long term memory memory retrieval nervous system disorder public health relevance relating to nervous system response selective attention

项目摘要

DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) plays a critical role in multiple cognitive processes. Dysfunction in the PFC has been implicated in a wide range of disorders including Alzheimer's disease, post-traumatic stress disorder, schizophrenia, and attention deficit hyperactivity disorder. Recent research has begun to focus on understanding how the PFC operates within functionally defined networks of brain structures. In particular, the PFC and medial temporal lobe areas such as the hippocampus may work together during the formation and retrieval of memory. This project will use trace fear conditioning (TFC) in laboratory rats as a model to understand the relative contributions of the PFC and hippocampus to the formation of new long-term memories. TFC differs from standard fear conditioning in that a small temporal gap, or "trace interval", is inserted between an auditory signal and an aversive outcome such as foot shock. Numerous studies have shown that normal learning in trace conditioning requires both the PFC and hippocampus, but the specific contributions of each structure as well as the principles by which they interact are currently not known. We will quantify the activity of intracellular signaling pathways known to be important for neural plasticity and learning within the PFC, hippocampus and amygdala in response to TFC training and determine how neural activity in one structure within this network affects responses in those connected to it. We will also determine the degree to which de novo protein synthesis within each brain area is required for the consolidation of a new TFC memory. This work represents the first systematic investigation of the molecular events required for memory formation in this network and one of very few studies to address the functional interactions between the PFC and hippocampus. PUBLIC HEALTH RELEVANCE: The prefrontal cortex (PFC) plays a critical role in multiple cognitive processes, and dysfunction in the PFC has been implicated in a wide range of disorders including Alzheimer's disease, post-traumatic stress disorder, schizophrenia, and attention deficit hyperactivity disorder. This study will provide important new data about how the PFC interacts with medial temporal lobe structures and about how molecular events in PFC neurons contribute to normal cognition.

描述(申请人提供)：前额叶皮质(PFC)在多种认知过程中起着关键作用。前额叶功能障碍与一系列疾病有关，包括阿尔茨海默病、创伤后应激障碍、精神分裂症和注意缺陷多动障碍。最近的研究已经开始集中于了解PFC如何在大脑结构的功能定义网络中运作。特别是，在记忆的形成和提取过程中，PFC和内侧颞叶区域，如海马体，可能会一起工作。该项目将使用实验室大鼠的痕迹恐惧条件反射(TFC)作为模型，以了解PFC和海马体对新的长期记忆形成的相对贡献。TFC与标准恐惧条件反射的不同之处在于，在听觉信号和令人厌恶的结果(如脚部电击)之间插入了一个小的时间间隔，即“痕迹间隔”。大量研究表明，在痕迹条件作用下的正常学习需要PFC和海马体，但每个结构的具体贡献以及它们相互作用的原理目前尚不清楚。我们将量化细胞内信号通路的活动，这些信号通路对TFC训练的PFC、海马体和杏仁核内的神经可塑性和学习至关重要，并确定该网络中一个结构中的神经活动如何影响与其连接的那些结构的反应。我们还将确定巩固新的TFC记忆所需的每个大脑区域内从头合成蛋白质的程度。这项工作是对这个网络中记忆形成所需的分子事件的第一次系统研究，也是为数不多的研究之一，以解决PFC和海马体之间的功能相互作用。公共卫生相关性：前额叶皮质(PFC)在多种认知过程中起着关键作用，PFC功能障碍与一系列疾病有关，包括阿尔茨海默病、创伤后应激障碍、精神分裂症和注意缺陷多动障碍。这项研究将提供关于PFC如何与内侧颞叶结构相互作用以及PFC神经元中的分子事件如何对正常认知做出贡献的重要新数据。