NMDA hypofunction and episodic memory: An animal model

NMDA 功能减退和情景记忆：动物模型

• 批准号: 8074007
• 负责人: JOSEPH T. COYLE
• 金额: $ 25.19万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8074007
• 关键词: Animal Model; Animals; Area; Behavioral; Cognitive; Computer Simulation; Development; Episodic memory; Event; Familiarity; Functional Imaging; Functional disorder; Hippocampus (Brain); Human; Knock-out; Laboratories; Lateral; Learning; Link; Measures; Mediating; Memory; Memory Disorders; Methodology; Modeling; Modification; Molecular Biology; Molecular and Cellular Biology; Mus; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Neurobehavioral Manifestations; Odors; Patients; Play; Protocols documentation; Psychotic Disorders; Rattus; Rodent Model; Role; Schizophrenia; Short-Term Memory; Stimulus; Symptoms; Techniques; Testing; animal model development; base; entorhinal cortex; experience; insight; memory recognition; memory retrieval; neuropsychological; novel; receptor function

This project will examine the hypothesis that NMDA receptor hypofunction within hippocampal regions model central features of the cognitive symptoms of schizophrenia. Neuropsychological studies in schizophrenic patients have identified a core deficit in episodic memory and studies on animals strongly suggest an essential role for NMDA receptors in the hippocampus is the storage and recall of associations that underlie our capacity for episodic memory. The proposed studies will combine our own recent development of a novel protocol for the assessment of specific features of episodic memory in animals and a novel technique for spatially and temporally selective NMDA receptor knockout developed in Robert Greene's laboratory. In collaborative studies we will explore the role of NMDA receptors in specific components of the hippocampal circuit. We expect to dissociate a critical role for NMDA receptors in area CA3 in the association of stimuli and their context from a critical role for NMDA receptors in area CA1 in memory for sequential events. We also expect to dissociate a critical role for CA3 and CA1 NMDA receptors in "all-or-none" episodic memory retrieval from a crucial role for NMDA receptors in the perirhinal and entorhinal cortex in recognition based on a sense of familiarity. Finally, we expect to identify a selective role for CA3 NMDA receptors in the linking of related memories supporting inferences from memory. These findings will provide insights about the functional circuitry of hippocampal NMDA receptors, of strong relevance to other center projects that employ functional imaging, molecular and cellular biology, and computational modeling.

该项目将研究海马区域内NMDA受体功能障碍的假设 精神分裂症认知症状的主要特征。精神分裂症的神经心理学研究 患者已经确定了情节记忆中的核心缺陷，对动物的研究强烈表明 NMDA受体在海马中的重要作用是基于的关联的存储和回忆 我们的情节记忆能力。拟议的研究将结合我们自己最近的发展 用于评估动物情节记忆的特定特征和新技术的新颖协议 对于在罗伯特·格林（Robert Greene）的实验室中开发的空间和时间选择性NMDA受体敲除。在 协作研究我们将探讨NMDA受体在海马特定组件中的作用 电路。我们期望将NMDA受体在CA3区域的刺激缔合中解散至关重要的作用 以及它们来自NMDA受体在区域CA1中的关键作用中的上下文。我们 还期望在“全或任何”情节记忆中分离CA3和CA1 NMDA受体的关键作用 从基于识别的基于识别的NMDA受体的关键作用中检索NMDA受体的关键作用 关于熟悉感。最后，我们希望在链接中确定CA3 NMDA受体的选择性作用 相关记忆，支持记忆的推论。这些发现将提供有关 海马NMDA受体的功能电路，与采用其他中心项目的强烈相关性 功能成像，分子和细胞生物学以及计算建模。