NMDA hypofunction and episodic memory: An animal model

本项目将检验海马区NMDA受体功能减退模型的假说 精神分裂症认知症状的中心特征。精神分裂症患者的神经心理学研究 患者已经发现情节记忆的核心缺陷，对动物的研究强烈表明 NMDA受体在海马体中的基本作用是存储和回忆潜在的联系 我们对情节记忆的能力。建议的研究将结合我们自己最近对 用于评估动物情节记忆特性的新方案和新技术 在空间和时间上选择性地敲除由罗伯特·格林实验室开发的NMDA受体。在……里面 合作研究我们将探索NMDA受体在海马区特定成分中的作用 巡回赛。我们期望解开CA3区NMDA受体在刺激联系中的关键作用。 以及它们的上下文来自于记忆中连续事件的CA1区NMDA受体的关键作用。我们 也希望分离CA3和CA1NMDA受体在“全有或全无”情节记忆中的关键作用 视网膜周围和内嗅觉皮质NMDA受体在再认中的关键作用 基于熟悉感。最后，我们希望确定CA3NMDA受体在连接中的选择性作用 支持从记忆中进行推理的相关记忆。这些发现将为我们提供关于 海马区NMDA受体的功能电路，与其他使用 功能成像、分子和细胞生物学以及计算建模。

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.