The Role of Oriens-Lacunosum Moleculare Interneurons in Sleep-Dependent Memory Consolidation

项目总结 睡眠和记忆之间的联系已经得到了很好的证实，尽管涉及的潜在机制还没有 完全理解。睡眠障碍对健康和认知有许多负面影响，本身就是 通常是精神和神经疾病的症状。对睡眠的作用有更全面的认识 在记忆加工中会加深我们对学习和记忆机制的认识 到潜在的干预领域，以改善疾病状态下的认知功能。这件事的首要目标是 该项目旨在增加我们对快速眼动睡眠及其在睡眠依赖中的作用的理解 通过描述东方腔隙分子(OLM)的必要性和作用进行巩固 在这种睡眠状态下，海马区的中间神经元。我们的初步数据表明，抑制所有 快速眼动睡眠期间背侧海马区生长抑素表达神经元导致记忆障碍 在新的物体放置识别(NOPR)和情境恐惧条件反射(CFC)任务中巩固。我们的 假说认为，OLM中间神经元活动对维持信息流的平衡至关重要。 在快速眼动睡眠期间，改变这些细胞的活动将导致 背景记忆巩固方面的缺陷。这项提案中概述的工作将建立在我们初步的 通过使用一种新的小鼠品系选择性地靶向OLM中间神经元来获得数据。在目标1中，我们将调查 快速眼动睡眠中刺激和抑制OLM细胞的行为效应 这是一项依赖海马体的记忆任务。我们将分析快速眼动睡眠中的OLM调制对 NOPR和CFC任务，并使用记录的LFP活动来研究睡眠结构和振荡活动。 目标2将确定在快速眼动睡眠期间调节OLM细胞活动对形成和 位置单元的维护。我们将使用光遗传学和体内钙成像相结合的方法来识别 放置单元并观察OLM单元调制如何影响放置单元特性，如场大小、触发 速度、稳定性和连贯性。完成这些目标将提供更多有关必要性的信息 REM睡眠对记忆巩固的作用，并确定OLM细胞在脑内局部海马区的作用。 空间记忆处理。实验将在吉娜·坡博士的实验室进行，吉娜·坡博士是睡眠和睡眠方面的专家 内存域。POE实验室在海马电生理学和啮齿动物睡眠方面的专业知识，以及 加州大学洛杉矶分校对开发神经技术的浓厚兴趣，使我在使用创新技术方面处于有利地位 调查这些问题的方法。下面描述的培训计划将强调建立强大的 通过统计和编程课程和研讨会的数据分析技能，在切割方面有坚实的基础- 通过实验和课程建议的边缘系统神经科学技术，以及拨款和 通过在不同场所展示和发表我的成果的机会，具有科学沟通能力。

PROJECT SUMMARY The link between sleep and memory is well-established, though the underlying mechanisms involved are not fully understood. Disordered sleep has numerous negative consequences to health and cognition, and is itself often a symptom of psychiatric and neurological illnesses. A more complete understanding of the role of sleep in memory processing will further our knowledge of the mechanisms of learning and memory, as well as point to potential areas for intervention to improve cognitive function in disease states. The overarching goal of this project is to increase our understanding of rapid eye movement (REM) sleep and its role in sleep-dependent consolidation through delineating the necessity and function of oriens-lacunosum moleculare (OLM) interneurons in the hippocampus during this sleep state. Our preliminary data suggest that inhibiting all somatostatin-expressing neurons in the dorsal hippocampus during REM sleep results in deficits in memory consolidation in novel object placement recognition (NOPR) and contextual fear conditioning (CFC) tasks. Our hypothesis is that OLM interneuron activity is crucial for maintaining the balance of information flow into the CA1 region of the hippocampus, and that changing the activity of these cells during REM sleep will result in deficits in contextual memory consolidation. The work outlined in this proposal will build upon our preliminary data through the use of a novel mouse line selectively targeting OLM interneurons. In Aim 1, we will investigate the behavioral effects of both stimulating and inhibiting OLM cells during REM sleep following the acquisition of a hippocampal-dependent memory task. We will analyze the effect of OLM modulation during REM sleep on both NOPR and CFC tasks and use recorded LFP activity to study sleep architecture and oscillatory activity. Aim 2 will determine the effect of modulating OLM cell activity during REM sleep on the formation and maintenance of place cells. We will use optogenetics in combination with in vivo calcium imaging to identify place cells and observe how OLM cell modulation impacts place cell characteristics such as field size, firing rate, stability, and coherence. Completion of these aims will provide more information regarding the necessity of REM sleep for memory consolidation, and define the role of OLM cells in local hippocampal circuits during spatial memory processing. Experiments will take place in the lab of Dr. Gina Poe, an expert in the sleep and memory field. The Poe lab's expertise in hippocampal electrophysiology and rodent sleep, together with UCLA's strong interest in developing neurotechnology, places me in a strong position to use innovative approaches to investigate these questions. The training plan described below will emphasize building strong data analysis skills through courses and workshops in statistics and programming, a solid foundation in cutting- edge systems neuroscience techniques through experiments and courses proposed, and grant-writing and scientific communication abilities through opportunities to present and publish my results in a variety of venues.