Neural representations of external stimuli in the lateral entorhinal cortex

描述(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。在这一过程中关键的大脑结构是海马体和内侧颞叶周围区域。尽管进行了数十年的密集研究，但海马体执行的精确电路机制和计算仍不清楚。尽管对海马体本身编码的表征知之甚少，但其中一个主要障碍是对海马体的两个主要皮质输入--内侧内嗅皮层(MEC)和外侧内嗅皮层(LEC)--的性质缺乏详细的了解。几年前，当在MEC中发现了“网格细胞”时，一个重大的突破出现了，它为在这个海马体传入中编码的表征提供了第一个确凿的句柄，并为开始理解将海马传入表征转化为其输出表征所涉及的计算奠定了基础。同时，我们的实验室也报道了LEC神经元的空间放电很少。也许，在我们对海马体处理的系统水平理解中，目前缺少的最关键的信息是阐明LEC中所代表的是什么。当大鼠研究环境中的个别物体时，LEC细胞是活跃的。本提案试图更深入地研究由LEC编码的这种外部刺激的表征的性质，以及这些表征如何被合并到海马区细胞的表征中。我们将使用多个Tetrode阵列记录行为大鼠的LEC、MEC和CA1以及CA3神经元群，以研究LEC浅层(向海马区发送投射)和深层(从海马区接受投射)的空间和非空间处理的性质。我们将测试这样一种假设，即当大鼠从事表示积极关注周围环境的行为时，LEC选择性地活跃(例如，在运动暂停时扫描头部的运动)，而当动物在其环境中从事探索性运动时，MEC选择性地活跃。我们将测试CA1和CA3是否在与大鼠头扫描行为相关的位置创建新的位置细胞，这表明来自LEC的外部信息整合到大鼠对其环境的内部空间表示中。由于人类内侧颞叶可能具有相似的位置和网格状特性，这些实验将有助于为了解人类的学习和记忆奠定基础，这对于开发治疗失忆症患者的方法至关重要，这些失忆症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。

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.