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: 8230497
• 负责人: JAMES J KNIERIM
• 金额: $ 41万
• 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/8230497
• 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. PUBLIC HEALTH RELEVANCE: Profound memory loss is a hallmark of such degenerative brain disorders as Alzheimer's Disease, which originates in an area called the entorhinal cortex, progresses into the hippocampus, and eventually progresses throughout the brain's cortical regions. The experiments in this proposal will address fundamental issues regarding the nature of information processing and functions in the entorhinal cortex and hippocampus, generating insight into how these brain regions work normally and how they may go awry when the regions are damaged by Alzheimer's disease, epilepsy, stroke, or traumatic injury.

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事件的长期记忆。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。尽管经过数十年的深入研究，海马体的精确电路机制和计算仍不清楚。尽管人们对海马体本身编码的表征了解很多，但主要障碍之一是缺乏对海马体的两个主要皮质输入，即内侧内嗅皮层（MEC）和外侧内嗅皮层（LEC）的特性的详细了解。几年前，当 MEC 中发现“网格细胞”时，出现了重大突破，为海马传入编码的表示提供了第一个可靠的处理，并为开始理解将海马传入表示转换为其输出表示所涉及的计算奠定了基础。与此同时，我们的实验室报告说，LEC 神经元几乎没有表现出空间放电。也许目前我们对海马处理的系统级理解中缺少的最关键的信息是对 LEC 中所代表内容的阐明。当大鼠研究环境中的单个物体时，LEC 细胞会处于活跃状态。本提案旨在更深入地研究 LEC 编码的此类外部刺激表征的性质，以及这些表征如何融入海马位置细胞表征中。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 浅层（将投影发送到海马体）和深层（接收来自海马体的投影）的空间和非空间处理的性质。我们将测试这样的假设：当大鼠进行表示积极关注周围环境的行为（例如运动暂停期间的头部扫描运动）时，LEC 会选择性地激活；而当动物在其环境中进行探索性运动时，MEC 会选择性地激活。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，这表明来自 LEC 的外部信息合并到了大鼠对其环境的内部空间表征中。由于人类内侧颞叶可能具有相似的位置和网格状特性，因此这些实验将有助于为理解人类学习和记忆奠定基础，这对于开发治疗健忘症患者的疗法至关重要，这些患者患有与阿尔茨海默病、颞叶癫痫和中风等疾病相关的毁灭性记忆丧失。 公共健康相关性：严重的记忆丧失是阿尔茨海默病等退行性脑部疾病的一个标志，这种疾病起源于一个称为内嗅皮层的区域，进展到海马体，并最终进展到整个大脑的皮质区域。该提案中的实验将解决有关内嗅皮层和海马体信息处理和功能性质的基本问题，深入了解这些大脑区域如何正常工作，以及当这些区域因阿尔茨海默病、癫痫、中风或外伤而受损时它们如何可能出错。