Sleep and Associative Memory Formation in Aplysia

海兔的睡眠和联想记忆的形成

• 批准号: 8771695
• 负责人: Lisa Carlson Lyons
• 金额: $ 22.8万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8771695
• 关键词: Acute; Adopted; Affect; Animal Model; Animals; Aplysia; Arousal; Aversive Stimulus; Behavior; Behavioral; Biological Assay; Cell physiology; Chronic; Circadian Rhythms; Development; Exhibits; Feeding behaviors; Food; Foundations; Functional disorder; Future; Gene Expression; Gene Expression Profile; Genes; Goals; Health; Hour; Human; In Situ Hybridization; Individual; Industrial Accidents; Injury; Invertebrates; Investigation; Jet Lag Syndrome; Learning; Location; Marines; Memory; Methods; Modeling; Molecular; Neuronal Plasticity; Neurons; Occupational; Occupational Accidents; Pathway interactions; Pattern; Performance; Plastics; Posture; Process; Productivity; Protein Isoforms; Proteins; RNA Sequences; Recording of previous events; Research; Rest; Short-Term Memory; Sleep; Sleep Deprivation; Sleep Disorders; Societies; System; Therapeutic; Traffic accidents; Training; Ubiquitin; Work; base; circadian pacemaker; cognitive function; cost; improved; in vivo; insight; long term memory; meetings; molecular dynamics; multicatalytic endopeptidase complex; neural circuit; neuronal circuitry; public health relevance; research study; response; shift work; social; therapy development; trafficking; transcriptome sequencing

DESCRIPTION (provided by applicant): Memory formation represents a dynamic process modulated by multiple factors including the circadian clock and sleep. In the past few decades, sleep loss and sleep deprivation have developed into major societal problems with individuals working longer hours, fragmented sleep patterns due to shift work, technological interferences and social jet lag. Sleep loss and sleep deprivation exact a heavy toll on society and individuals through increased traffic accidents, increased industrial and occupational accidents, and decreased productivity and performance. Sleep deprivation causes significant decrements in short and long-term memory. In order to ameliorate the consequences of sleep deprivation, it is necessary to understand how systems level problems and changes in behavior affect molecular and cellular processes at the level of individual neuronal circuits and neuron groups. Defining the mechanisms through which sleep and sleep loss impact memory formation is crucial to identifying methods to optimize performance and health in modern society. Given the high molecular conservation underlying memory formation across species, the marine mollusk Aplysia californica with its simple neural circuitry provides an ideal model for detailing in vivo interactions between sleep, the circadian clock and memory. Previously, we described short, intermediate and long-term memory for an operant learning paradigm, learning that food is inedible (LFI). We have characterized sleep in Aplysia and found that Aplysia sleep patterns resemble human sleep patterns with sleep occurring only at night in long consolidated bouts. Our long-term objective is to define the mechanisms through which the sleep deprivation affects the formation of associative memories and identify mechanisms through which the circadian clock and sleep interact to regulate memory. The goal of this proposal is to identify cellular changes and changes in gene expression caused by sleep deprivation specifically in the neurons involved in feeding behaviors and LFI memory and to identify genes and pathways necessary for long-term memory formation that are inhibited by sleep deprivation. These studies will further our understanding of the functions of sleep and importantly, provide a research base for future therapeutic treatments to improve memory and performance.

描述（由申请人提供）：记忆形成表示由包括生物钟和睡眠的多个因素调节的动态过程。在过去的几十年里，睡眠不足和睡眠剥夺已经发展成为主要的社会问题，个人工作时间更长，由于轮班工作，技术干扰和社会时差造成的睡眠模式碎片化。睡眠不足和睡眠剥夺通过增加交通事故，增加工业和职业事故，以及降低生产力和表现，对社会和个人造成严重影响。睡眠不足会导致短期和长期记忆的显著下降。为了改善睡眠剥夺的后果，有必要了解系统水平的问题和行为变化如何影响单个神经元回路和神经元组水平的分子和细胞过程。确定睡眠和睡眠不足影响记忆形成的机制对于确定优化现代社会表现和健康的方法至关重要。考虑到跨物种记忆形成的高分子保守性，海洋软体动物加州龙蜥及其简单的神经回路提供了一个理想的模型，用于详细说明睡眠，昼夜节律钟和记忆之间的体内相互作用。以前，我们描述了短期，中期和长期记忆的操作性学习范式，学习食物是不可食用的（LFI）。我们已经描述了失智症患者的睡眠特征，发现失智症患者的睡眠模式类似于人类的睡眠模式，睡眠只发生在夜间，并且是长时间的巩固发作。我们的长期目标是确定睡眠剥夺影响联想记忆形成的机制，并确定生物钟和睡眠相互作用调节记忆的机制。该提案的目标是确定由睡眠剥夺引起的细胞变化和基因表达变化，特别是在涉及摄食行为和LFI记忆的神经元中，并确定睡眠剥夺抑制长期记忆形成所需的基因和途径。这些研究将进一步加深我们对睡眠功能的理解，更重要的是，为未来改善记忆和表现的治疗提供研究基础。