Prefrontal and Medial-Temporal Interactions in Memory

描述（由申请人提供）：神经科学的一个基本挑战是理解大脑主要区域如何作为一个系统一起运作以支持高水平的认知功能。特别是，一个对理解精神障碍非常重要的系统涉及前额叶皮层（PFC）和内侧颞叶（MTL），它们都有助于记忆和认知的高级功能。近年来，在揭示PFC和MTL内各个区域的单独功能方面取得了重大进展，并在显示这些区域协同工作方面取得了一些成功。然而，关于PFC和MTL在记忆和认知服务中的相互作用机制的知识缺乏。在这里，我们汇集了一组研究人员，他们领导了PFC和MTL的研究，或两者兼而有之，使用不同的方法和不同的物种。我们合作开发了PFC-MTL相互作用的假设，旨在整合我们的优势，揭示这种相互作用的机制，并在这样做时，开创了对记忆和认知的真正系统级理解。我们的策略结合了PFC和MTL功能的理论，并结合了我们团队的协调实验分析，这些分析汇聚在一个共同的行为范式上，用于探索上下文引导的联想记忆中的编码和检索操作。实验项目将使用多种交叉的方法来研究PFC和MTL区域如何单独和相互作用：在人类中，使用脑损伤个体的神经心理学研究和正常人类受试者的功能磁共振成像，在猴子中使用单个神经元活动和局部场电位的神经生理学研究，在大鼠中使用非空间和空间记忆的联合神经生理学和可逆失活研究。研究结果将通过两种关键方式进行整合，一种是通过分析核心直接比较不同的数据模式，另一种是通过融合到一个计算模型中，该模型提供了PFC-MTL相互作用的全面统一说明。该中心还将追求几个直接相关的教育、传播和外展目标。

DESCRIPTION (provided by applicant): A fundamental challenge in neuroscience is understanding of how major brain areas operate together as a system to support high level cognitive functions. In particular, one system of great importance to the understanding of mental disorders involves the prefrontal cortex (PFC) and the medial temporal lobe (MTL) that each contribute to high level functions in memory and cognition. In recent years, there has been significant progress in revealing the individual functions of areas within the PFC and MTL, and some successes in showing that these areas work together. However, there is a paucity of knowledge about the mechanisms by which PFC and MTL interact in the service of memory and cognition. Here we bring together a group of investigators who have led research on PFC and MTL, or both, using diverse approaches and different species. We have collaborated to develop an hypothesis of PFC-MTL interactions and aim to integrate our strengths towards revealing the mechanisms of that interaction, and in so doing, pioneer a true systems level understanding of memory and cognition. Our strategy combines theories of PFC and MTL function generated by our group with coordinated experimental analyses that converge on a common behavioral paradigm for exploring encoding and retrieval operations in context-guided associative memory. Experimental projects will examine how PFC and MTL areas contribute individually and interactively, using diverse and intersecting approaches: in humans, using both neuropsychological studies of brain damaged individuals and fMRI on normal human subjects, in monkeys using neurophysiological studies of single neuron activity and local field potentials, in rats using combined neurophysiological and reversible inactivation studies of non-spatial and spatial memory. The findings will be integrated in two key ways, by direct comparison of different data modalities through an Analysis Core and by convergence into a computational model that provides a comprehensive and unified account of PFC-MTL interactions. The Center will also pursue several directly related educational, dissemination, and outreach goals. PUBLIC HEALTH RELEVANCE: PFC and MTL areas are implicated in a broad range of mental disorders. Moreover, it has become increasingly clear that aspects of mental disorders reflect a breakdown of network functions of the PFC-MTL system. Correspondingly, characterization of PFC-MTL interactions is fundamental to understanding the origins of mental disorders and to developing therapies that influence network-level information processing.