Prospective Coding and Memory Retrieval

前瞻性编码和记忆检索

基本信息

项目摘要

DESCRIPTION (provided by applicant): Memory's purpose is to guide adaptive behavior: we recall the past to inform the present, to anticipate the outcome of choices, and thereby guide goal-directed responses. To be useful, memory retrieval must be selective, directed by the salient features of situations, and flexible to adapt to changing internal goals, environmental opportunities, and potential actions. The hippocampus and the orbital prefrontal cortex (OFC) are crucial for different aspects of adaptive behavior, and dysfunction of either of these brain regions can contribute to neuropsychiatric disorders including Alzheimer's disease, PTSD, and schizophrenia. This proposal will investigate how the OFC and the hippocampus contribute to flexible, goal-directed, memory guided behavior. The experiments, part of a larger research program on how prefrontal cortex contributes to memory, will test the general hypothesis that bidirectional interactions between OFC and hippocampal circuits provide key mechanisms for selective retrieval of goal-related representations by integrating reward history and memory for episodes. The specific aims will investigate these mechanisms by combining behavior analysis, temporary inactivation, simultaneous recording of neuronal activity in both structures, and deep brain stimulation (DBS). Aim 1 will assess the functional interactions between the two structures during learning and memory retrieval. Rats will be trained in a + maze task that either requires one structure, the other, both, or neither. Interactions between the structures will be tested by temporarily disrupting one, the other, or both on opposite sides of the brain. If OFC-hippocampal interactions are required for flexible memory retrieval, then the "crossed inactivation" should produce similar impairments as bilateral inactivation. Aim 2 will record neuronal activity in both structures simultaneously to determine how activity within and between the OFC and hippocampus predict learning and memory performance. We recently identified EEG patterns in the hippocampus that predicted memory retrieval, and discovered that DBS could both mimic these patterns and restore memory in otherwise amnestic animals. Aim 3 will therefore test the causal relationships between the OFC and hippocampus by combining temporary inactivation, dual recordings, and DBS. Recording one structure while disrupting activity in the other will determine the extent to which normal coding in each structure depends on the other,and how these interactions influence learning and memory. Targetted patterns of DBS will be used to mimic identified signals within and between hippocampal and OFC circuits to determine if the effects of inactivation can be overcome, or normal performance enhanced. The outcome will advance neuroscience by revealing how the OFC and hippocampus interact to guide flexible and selective use of memory, and will inform emerging treatments for behavioral and neuropsychiatric disorders that involve disintegration of prefrontal cortex and hippocampal functions, including schizophrenia and Alzheimer's disease.
描述(由申请人提供):记忆的目的是指导适应性行为:我们回忆过去以告知现在,预测选择的结果,从而指导目标导向的反应。为了发挥作用,记忆检索必须是有选择性的,以情况的显着特征为指导,并且灵活地适应不断变化的内部目标、环境机会和潜在行动。海马体和眶前额叶皮层 (OFC) 对于适应性行为的不同方面都至关重要,这两个大脑区域的功能障碍都可能导致神经精神疾病,包括阿尔茨海默病、创伤后应激障碍和精神分裂症。该提案将研究 OFC 和海马体如何促进灵活的、目标导向的、记忆引导的行为。这些实验是关于前额叶皮层如何促进记忆的大型研究计划的一部分,将测试以下一般假设:OFC 和海马回路之间的双向相互作用通过整合奖励历史和事件记忆,为选择性检索目标相关表征提供了关键机制。具体目标将通过结合行为分析、暂时失活、同时记录两个结构中的神经元活动以及深部脑刺激(DBS)来研究这些机制。目标 1 将评估学习和记忆检索过程中两种结构之间的功能相互作用。老鼠将接受迷宫任务的训练,该任务要么需要一种结构,要么需要另一种结构,要么两者都需要,或者两者都不需要。将通过暂时扰乱大脑相对侧的一个、另一个或两者来测试这些结构之间的相互作用。如果灵活的记忆检索需要 OFC-海马相互作用,那么“交叉失活”应该产生与双边失活类似的损伤。目标 2 将同时记录两个结构中的神经元活动,以确定 OFC 和海马体内部和之间的活动如何预测学习和记忆表现。我们最近发现了海马体中预测记忆检索的脑电图模式,并发现 DBS 既可以模仿这些模式,又可以恢复失忆动物的记忆。因此,目标 3 将通过结合暂时失活、双重记录和 DBS 来测试 OFC 和海马体之间的因果关系。记录一种结构,同时破坏另一种结构的活动,将决定每种结构中正常编码对另一种结构的依赖程度,以及这些相互作用如何影响学习和记忆。 DBS 的目标模式将用于模拟海马和 OFC 回路内部和之间已识别的信号,以确定是否可以克服失活的影响或增强正常性能。该结果将通过揭示 OFC 和海马如何相互作用来指导灵活和选择性的记忆使用来推进神经科学,并将为涉及前额皮质和海马功能解体的行为和神经精神疾病(包括精神分裂症和阿尔茨海默病)的新兴治疗提供信息。

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Matthew L Shapiro其他文献

Matthew L Shapiro的其他文献

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{{ truncateString('Matthew L Shapiro', 18)}}的其他基金

Learning, Prefrontal Cortex, and Multiple Memory Systems
学习、前额皮质和多重记忆系统
  • 批准号:
    8632057
  • 财政年份:
    2014
  • 资助金额:
    $ 40.56万
  • 项目类别:
Learning, Prefrontal Cortex, and Multiple Memory Systems
学习、前额皮质和多重记忆系统
  • 批准号:
    9222048
  • 财政年份:
    2014
  • 资助金额:
    $ 40.56万
  • 项目类别:
PFC-MTL FUNCTIONAL INTERACTIONS IN SPATIAL MEMORY
空间记忆中的 PFC-MTL 功能相互作用
  • 批准号:
    8303575
  • 财政年份:
    2011
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective memory coding by the hippocampus
海马体的前瞻性记忆编码
  • 批准号:
    7355971
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective memory coding by the hippocampus
海马体的前瞻性记忆编码
  • 批准号:
    7033346
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective Coding and Memory Retrieval
前瞻性编码和记忆检索
  • 批准号:
    9904758
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective Coding and Memory Retrieval
前瞻性编码和记忆检索
  • 批准号:
    10323036
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective Coding and Memory Retrieval
前瞻性编码和记忆检索
  • 批准号:
    8974442
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective Coding and Memory Retrieval
前瞻性编码和记忆检索
  • 批准号:
    8501739
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:
Prospective memory coding by the hippocampus
海马体的前瞻性记忆编码
  • 批准号:
    7569011
  • 财政年份:
    2006
  • 资助金额:
    $ 40.56万
  • 项目类别:

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