NMDA hypofunction and episodic memory: An animal model

本研究将探讨海马区NMDA受体功能低下的模型 精神分裂症认知症状的核心特征精神分裂症患者的神经心理学研究 患者已经确定了情节记忆的核心缺陷，对动物的研究强烈表明， 海马中NMDA受体的重要作用是存储和回忆相关信息， 我们的情景记忆能力拟议的研究将结合我们自己最近开发的一种联合收割机， 评估动物情景记忆特定特征的新方案和新技术 用于空间和时间选择性NMDA受体敲除，该技术是在Robert格林的实验室开发的。在 合作研究，我们将探讨NMDA受体在海马的特定组成部分的作用， 电路.我们希望能分离出CA3区NMDA受体在刺激关联中的关键作用 和他们的背景下，从一个关键的作用，NMDA受体在CA1区的记忆顺序事件。我们 我还希望能分离出CA3和CA1 NMDA受体在“全有或全无”情景记忆中的关键作用 检索从一个至关重要的作用，NMDA受体在周围和内嗅皮层的识别为基础 一种熟悉感。最后，我们希望确定CA3 NMDA受体在连接中的选择性作用。 相关的记忆支持从记忆中推断。这些发现将提供有关 海马NMDA受体的功能电路，与其他中心项目密切相关， 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.