Dynamic Analysis of Neural Plasticity in the Hippocampal Circuit

描述（由申请人提供）：海马体的形成对于存储某些类型的记忆至关重要，包括人类对事实和事件的记忆以及啮齿动物对空间的记忆。了解海马体在学习中的作用是一个复杂的问题，部分原因是海马体不是一个单一的区域，而是由几个区域组成，包括内嗅皮层（EC）、齿状回（DG）、CA3、CA1和下托，每个区域在学习过程中都可能发挥独特的作用。此外，学习本身就是一种涉及多种行为和认知成分的复杂现象。因此，挑战在于超越讨论海马体和学习的简写，而是开始研究海马体回路中每个区域在复杂任务的学习和表征中的作用。对于空间任务，我们必须认识到学习有多个组成部分，包括对特定空间位置的学习以及对认知任务结构的学习。对空间的学习和对任务的学习可能发生在相同的区域，也可能发生在回路中非常不同的位置。我们的主要目标之一是探索空间和任务相关学习的神经基础。我们将使用行为学、电生理学和先进的分析技术来识别空间和任务相关的神经活动的性质以及海马回路的可塑性。本研究的具体目的是：(1)验证在学习过程中，海马体结构的可塑性改变了海马体神经元的位置和θ相关反应的假设；(2)验证海马体结构内的每个区域都表现出与新空间表征形成相关的不同的神经动力学模式的假设。3)为了验证海马体结构内的每个区域显示与任务相关信息编码相关的不同神经动力学模式的假设。我们的首要假设是，海马体中新表征的形成是一个渐进的过程，表征在输入和输出区域迅速建立起来，然后作为回路内处理的结果而具体化。这项工作将超越以往的研究，研究神经动力学在学习新地方和新任务的基础上。了解海马体如何参与学习可能有助于我们制定新的策略来治疗与海马体功能障碍相关的精神障碍患者，包括患有精神分裂症的个体以及患有学习障碍的儿童和成人。对海马体回路可塑性的研究也可以帮助我们理解与异常可塑性相关的疾病，如癫痫。

DESCRIPTION (provided by applicant): The hippocampal formation is essential for the storage of certain types of memories, including memories for facts and events in humans and memories for space in rodents. Understanding the role of the hippocampus in learning is a complex problem, in part because the hippocampus is not a single region but is instead made of up several areas, including the entorhinal cortex (EC), dentate gyrus (DG), CA3, CA1 and the subiculum, each of which may play a unique role in this process. In addition, learning is itself a complex phenomenon involving multiple behavioral and cognitive components. The challenge, then, is to go beyond the shorthand of discussing the hippocampus and learning and instead begin to examine the role of each area within the hippocampal circuit in the learning and representation of complex tasks. For spatial tasks we must recognize that there are multiple components to learning, including learning about the specific spatial locations as well as learning about the structure of the cognitive task. Learning about space and learning about task could occur in the same regions, or could occur at very different sites in the circuit. One of our major goals is to explore the neural bases of both spatial and task-related learning. We will use behavioral, electrophysiological and advanced analytical techniques to identify the nature of spatial and task-related neural activity and plasticity across the hippocampal circuit. The Specific Aims of this proposal are 1) To test the hypothesis that during learning, plasticity in the hippocampal formation changes the place and theta related responses of hippocampal neurons, 2) To test the hypothesis that each region within the hippocampal formation shows a distinct pattern of neural dynamics associated with the formation of new spatial representations, 3) To test the hypothesis that each region within the hippocampal formation shows a distinct pattern of neural dynamics associated with the encoding of task related information. Our overarching hypothesis is that the formation of new representations in the hippocampus is an incremental process, where representations are quickly established in the input and output regions and then elaborated as a result of processing within the circuit. This work will go beyond previous studies to examine the neural dynamics that underlie learning about new places and new tasks. Understanding how the hippocampus participates in learning may help us develop new strategies for treating people with mental impairments related to hippocampal dysfunction, including individuals suffering from schizophrenia as well as children and adults with learning impairments. The study of plasticity in the hippocampal circuit may also help us understand disorders related to abnormal plasticity such as epilepsy.