Neural representations of external stimuli in the lateral entorhinal cortex

外侧内嗅皮层外部刺激的神经表征

• 批准号: 8402408
• 负责人: JAMES J KNIERIM
• 金额: $ 39.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8402408
• 关键词: Address; Alzheimer' s Disease; Animals; Area; Attention; Back; Behavior; Binding; Brain; Brain Diseases; Brain region; Cells; Cognitive; Conscious; Cues; Data; Development; Disease; Distal; Environment; Epilepsy; Episodic memory; Event; Feedback; Fire - disasters; Foundations; Head; Hippocampus (Brain); Human; Individual; Injury; Knowledge; Laboratories; Lateral; Learning; Location; Locomotion; Maps; Medial; Memory; Memory Loss; Movement; Nature; Neocortex; Neurons; Organism; Output; Pathway interactions; Perforant Pathway; Periodicity; Population; Positioning Attribute; Prevalence; Process; Property; Pyramidal Cells; Rattus; Reporting; Research; Rodent; Scanning; Sensory; Signal Transduction; Specificity; Stimulus; Stroke; Structure; System; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Time; Visit; Work; base; cognitive neuroscience; entorhinal cortex; experience; information processing; insight; long term memory; public health relevance; relating to nervous system; research study; theories; therapy development

DESCRIPTION (provided by applicant): One of the key questions in cognitive neuroscience is how the brain constructs and stores long-term memories of autobiographical events. The critical brain structures in this process are the hippocampus and surrounding regions of the medial temporal lobe. Despite decades of intensive research, the precise circuit mechanisms and computations performed by the hippocampus remain unclear. Although much is known about the representations encoded by the hippocampus proper, one of the major impediments has been a lack of detailed knowledge of the properties of the two major cortical inputs to the hippocampus, the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). A major breakthrough occurred a few years ago when the "grid cell" was discovered in the MEC, providing the first firm handle on the representations encoded in this hippocampal afferent and a basis for beginning to understand the computations involved in transforming hippocampal afferent representations into its output representations. At the same time, our laboratory reported that LEC neurons displayed little spatial firing. Perhaps the most critical piece of information presently missing in our systems-level understanding of hippocampal processing is an elucidation of what is represented in the LEC. LEC cells are active when the rat investigates individual objects in an environment. The present proposal seeks to investigate in greater depth the nature of the representations of such external stimuli encoded by the LEC and how these representations become incorporated into the hippocampal place cell representation. We will use multiple tetrode arrays to record from populations of LEC, MEC, and CA1, and CA3 neurons in behaving rats to investigate the nature of spatial and nonspatial processing in the superficial layers of the LEC (which send projections into the hippocampus) and the deep layers (which receive projections from the hippocampus). We will test the hypothesis that the LEC is selectively active when the rat is engaged in behaviors denoting active attention to its surroundings (such as head- scanning movements during pauses in locomotion) and the MEC is selectively active when the animal is engaged in exploratory movements through its environment. We will test whether CA1 and CA3 create new place cells at locations associated with the rat's head-scanning behavior, suggesting the incorporation of external information from LEC into the rat's internal spatial representation of its environment. Because the human medial temporal lobe is likely to have similar place and grid-like properties, these experiments will help lay the foundation for understanding human learning and memory, which is critical for developing therapies for amnesic individuals that suffer from the devastating memory loss associated with such disorders as Alzheimer's Disease, temporal lobe epilepsy, and stroke.

描述（由申请人提供）：认知神经科学的关键问题之一是大脑如何构建和存储自传体事件的长期记忆。在这个过程中，关键的大脑结构是海马体和内侧颞叶的周围区域。尽管经过了几十年的深入研究，海马体执行的精确电路机制和计算仍然不清楚。虽然我们对海马体编码的表征有很多了解，但主要的障碍之一是对海马体的两个主要皮质输入（内侧内嗅皮质（MEC）和外侧内嗅皮质（LEC））的特性缺乏详细的了解。几年前，当MEC中的"网格细胞"被发现时，出现了一个重大突破，这为海马传入神经编码的表征提供了第一个可靠的处理方法，并为开始理解将海马传入表征转换为输出表征所涉及的计算奠定了基础。同时，我们的实验室报道LEC神经元几乎没有空间放电。也许，在我们对海马加工的系统水平的理解中，目前缺少的最关键的信息是阐明LEC中所代表的内容。当大鼠研究环境中的单个物体时，LEC细胞是活跃的。本建议旨在更深入地调查的性质，这种外部刺激的编码LEC和这些表示如何成为纳入海马位置细胞的代表。我们将使用多个四极阵列记录行为大鼠的LEC、MEC、CA1和CA3神经元群体，以研究LEC表层（将投射发送到海马）和深层（接收来自海马的投射）的空间和非空间处理的性质。我们将测试这样的假设，即当大鼠从事表示对其周围环境的主动注意的行为（例如在运动暂停期间的头部扫描运动）时，LEC是选择性活跃的，并且当动物从事通过其环境的探索运动时，MEC是选择性活跃的。我们将测试CA1和CA3是否在与大鼠头部扫描行为相关的位置创建新的位置细胞，这表明将LEC的外部信息纳入大鼠对其环境的内部空间表征。由于人类内侧颞叶可能具有类似的位置和网格状属性，这些实验将有助于为理解人类学习和记忆奠定基础，这对于开发与阿尔茨海默病，颞叶癫痫和中风等疾病相关的毁灭性记忆丧失的健忘症患者的治疗方法至关重要。