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Learning, Prefrontal Cortex, and Multiple Memory Systems

学习、前额皮质和多重记忆系统

基本信息

批准号：
8632057
负责人：
Matthew L Shapiro
金额：
$ 41.76万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8632057
关键词：
Adaptive Behaviors Alzheimer&apos s Disease Animals Behavior Behavioral Bilateral Biological Neural Networks Brain Brain region Cannulas Cells Code Cognition Corpus striatum structure Cues Deep Brain Stimulation Dementia Discrimination Disease Electroencephalography Environment Event Expectancy Fire - disasters Functional disorder Goals Hippocampus (Brain)Impairment Infusion procedures Ipsilateral Learning Light Location Medial Memory Mental Depression Methods Muscimol Neostriatum Neurology Neurons Neurosciences Outcome Pattern Performance Physiological Post-Traumatic Stress Disorders Prefrontal Cortex Psychiatry Rattus Recording of previous events Research Response to stimulus physiology Rewards Role Schizophrenia Shapes Side Signal Transduction Staging Stimulus Structure System Temporal Lobe Testing Time Training Viral Vector Visual abstracting arm base experience flexibility habit learning improved insight memory retrieval mental set neuropsychiatry novel optogenetics prevent programs prospective public health relevance relating to nervous system research study response

项目摘要

Learning, Prefrontal Cortex, and Multiple Memory Systems Learning, to be useful, must be sensitive to the relevant features of situations, guided by environmental opportunities, and informed by past actions in similar circumstances. In other words, learning is guided by memory. The neuronal mechanisms that integrate learning and memory are largely unknown. The hippocampus is crucial for learning facts and remembering events, the neostriatum is important for habit learning, and the prefrontal cortex (PFC) is needed to modify previously learned responses flexibly. Dysfunction of each of these brain regions or their disconnection contributes to neuropsychiatric disorders including dementia, PTSD, and schizophrenia. This proposal will investigate how these structures interact during memory-guided learning. The experiments, part of a larger research program on how prefrontal cortex contributes to memory and cognition, will test the hypothesis that interactions between PFC, hippocampal and dorsolateral striatal (DLS) circuits provide key mechanisms for memory guided learning by integrating abstract rules, event sequences, and stimulus-directed actions. The specific aims will investigate these mechanisms by combining behavior analysis, temporary inactivation, simultaneous recording of neuronal activity, and deep brain stimulation. Aim 1 will assess the functional interactions between the PFC, hippocampus, and DLS the during learning by temporary disruption of local circuits. Rats will be trained to two behaviorally identical + maze tasks, one that requires the hippocampus, the other the DLS for initial learning~ the PFC is needed to switch between them. Interactions between the PFC and the other structures will be tested by temporarily the mPFC and one of the other structures both the on opposite side of the brain. If PFC interactions are required for flexible learning, then the "crossed inactivation" should produce asymmetric impairments in switching from one strategy to the other. Aim 2 will record neuronal activity in the three structures simultaneously to determine how activity within and between the PFC and the other structures predict learning. 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 PFC and the other structures by combining unilateral inactivation, bilateral recordings, and DBS. Recording in PFC while disrupting activity unilaterally in the hippocampus or DLS, or vice versa, will determine the extent to which normal coding in each structure depends on the other, and how these interactions influence learning. Targetted patterns of DBS will be used to mimic identified signals within and between circuits to determine if the effects of inactivation can be overcome, or learning strategy modified. The outcome will advance neuroscience by revealing how the PFC, hippocampus, and DLS interact to allow memory-guided learning, and will inform emerging treatments for neuropsychiatric disorders that involve disintegration of prefrontal cortex, hippocampal, and striatal functions, including schizophrenia and Alzheimer's disease.

学习、前额皮质和多重记忆系统学习若要有用，必须对情境的相关特征敏感，并以环境为指导机会，并通过类似情况下过去的行动来了解。换句话说，学习是由记忆。整合学习和记忆的神经机制在很大程度上是未知的。这海马体对于学习事实和记忆事件至关重要，新纹状体对于习惯很重要学习过程中，需要前额皮质（PFC）来灵活地修改先前学到的反应。这些大脑区域的功能障碍或它们的断开会导致神经精神疾病包括痴呆症、创伤后应激障碍和精神分裂症。该提案将研究这些结构如何相互作用在记忆引导学习过程中。这些实验是一项更大的研究计划的一部分，该研究计划旨在研究前额皮质如何有助于记忆和认知，将检验 PFC、海马和背外侧纹状体 (DLS) 回路通过整合抽象信息为记忆引导学习提供关键机制规则、事件序列和刺激导向的行动。具体目标将通过以下方式研究这些机制：结合行为分析、暂时失活、神经元活动同步记录和深度分析大脑刺激。目标 1 将评估 PFC、海马体和 DLS 之间的功能相互作用在学习期间，局部电路暂时中断。老鼠将被训练成两种行为相同的+ 迷宫任务，一个需要海马，另一个需要DLS进行初始学习~需要PFC 在它们之间切换。 PFC 与其他结构之间的相互作用将通过临时测试 mPFC 和其他结构之一都位于大脑的另一侧。如果需要 PFC 交互对于灵活的学习，那么“交叉失活”应该在从一种策略对另一种策略的影响。目标 2 将同时记录三个结构中的神经元活动以确定前额皮质和其他结构内部以及之间的活动如何预测学习。我们最近发现脑电图海马体中预测记忆检索的模式，并发现 DBS 可以模仿这些模式模式并恢复失忆动物的记忆。因此，目标 3 将测试因果关系通过结合单侧失活、双边记录和 DBS 来在 PFC 和其他结构之间建立联系。在 PFC 中记录，同时单方面扰乱海马或 DLS 的活动，反之亦然，将确定每个结构中的正常编码在多大程度上依赖于另一个结构，以及这些相互作用如何影响学习。 DBS 的目标模式将用于模拟电路内部和电路之间的已识别信号，以确定是否可以克服失活的影响，或修改学习策略。结果将通过揭示 PFC、海马体和 DLS 如何相互作用以允许记忆引导来推进神经科学学习，并将为涉及神经精神疾病瓦解的新兴治疗方法提供信息前额皮质、海马和纹状体功能，包括精神分裂症和阿尔茨海默病。