Linking Hippocampal Replay Content to Learning and Decision-Making

项目总结/摘要 记忆是人类认知的一个组成部分，当记忆过程出错时， 记忆丧失的毁灭性神经系统疾病，包括阿尔茨海默病和其他形式的痴呆症。 正常记忆过程的一个重要作用是利用以前的经验来指导对未来的决定。 行动因此，研究确定记忆过程的神经机制对于理解两者都很重要。 正常的大脑功能和记忆丧失障碍的问题。此外，这些研究的见解可以 帮助开发治疗这些疾病的新方法。最近的研究表明，同步的神经元放电事件， 在清醒不动期间发生的海马体称为尖波波纹（SWR）， 学习空间记忆任务。SWR通常包含特定的位置细胞放电序列， 类似于在先前经历中的放电（“重放”事件），这表明了一种潜在的神经机制， 特定的先前经历。然而，并非所有清醒的SWR都包含编码体验的重放事件 与当前环境相关，因此是否需要重放的特定内容用于学习仍然存在 一个没有答案的问题我假设特定于内容的重放事件用于检索特定的先前事件， 学习和决策都需要经验。到目前为止，这一假设还没有直接 测试和缺乏测试是我们理解记忆过程的神经机制的一个主要差距。在 初步工作，我已经开发了一个系统，解码和分类重放事件的实时，可以 基于重放事件的内容提供行为或神经反馈。我将用这个系统来测试三个 相关假设，（1）重放内容可以通过行为条件反射进行调节，（2）特定重放内容 可以驱动行为，以及（3）学习需要特定的重放内容。除了这些实验，我 奖学金培训计划包括研究和学术目标。我的研究目标是研究 记忆过程的神经机制，并学习体内生理学和计算方法 神经科学我的学术目标是在计算神经科学方面打下坚实的基础， 提高我在奖学金结束时向独立过渡所需的职业发展技能。 我的赞助人洛伦·弗兰克和共同赞助人乌里·伊登的实验室以及加州大学旧金山分校的科学界 将提供良好的培训环境。弗兰克博士是慢性海马神经系统疾病领域的领先专家 记录和神经数据分析方法。伊登博士是计算和理论方法方面的专家 神经科学，包括我将在实验中使用的算法。加州大学旧金山分校是一个首屈一指的学术研究 医学和神经生物学机构，重点关注合作和丰富的职业发展 博士后研究员的资源。

PROJECT SUMMARY / ABSTRACT Memory is an integral component of human cognition, and when memory processes go awry, the result is devastating neurological disorders of memory loss including Alzheimer's disease and other forms of dementia. One essential role of normal memory processes is to use previous experience to guide decisions about future actions. Thus, research to define the neural mechanisms of memory processes is important to understand both normal brain function and what goes wrong in memory loss disorders. Further, insights from these studies could help develop new treatments for these disorders. Recent work showed that synchronized neuron firing events in the hippocampus called sharp wave ripples (SWRs) that occur during awake immobility are required for rapid learning during spatial memory tasks. SWRs often contain specific place-cell firing sequences that closely resemble firing during prior experiences (“replay” events), suggesting a potential neural mechanism for retrieval of specific prior experiences. However, not all awake SWRs contain replay events that encode experiences related to the current environment, and so whether the specific content of replay is required for learning remains an unanswered question. I hypothesize that content-specific replay events serve to retrieve specific prior experiences and so are required for learning and decision-making. To date, this hypothesis has not been directly tested and the lack of tests is a major gap in our understanding of neural mechanisms of memory processes. In preliminary work, I have developed a system that decodes and classifies replay events in real-time and can provide behavioral or neural feedback based on the content of a replay event. I will use this system to test three related hypotheses, (1) replay content can be modulated by behavioral conditioning, (2) specific replay content can drive behavior, and (3) specific replay content is required for learning. In addition to these experiments, my fellowship training plan includes research and academic goals. My research goals are to investigate fundamental neural mechanisms of memory processes and to learn the methods of in vivo physiology and computational neuroscience. My academic goals are to build a strong foundation in computational neuroscience and continue to improve the career development skills I will need for my transition to independence at the end of this fellowship. Together, the labs of my sponsor, Loren Frank, and co-sponsor, Uri Eden, and the UCSF scientific community will provide an excellent training environment. Dr. Frank is a leading expert in the field of chronic hippocampal recording and neural data analysis methods. Dr. Eden is an expert in methods of computational and theoretical neuroscience, including the algorithms I will use in my experiments. UCSF is a premier academic research institution for medicine and neurobiology with a strong focus on collaboration and plentiful career development resources for postdoctoral fellows.