Sleep and Associative Memory Formation in Aplysia

描述（由申请人提供）：记忆的形成是一个受生物钟和睡眠等多种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，轮班工作导致的睡眠模式碎片化，技术干扰和社交时差。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，对社会和个人造成了沉重的代价。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群水平的分子和细胞过程。定义睡眠和睡眠不足影响记忆形成的机制对于确定在现代社会中优化表现和健康的方法至关重要。考虑到跨物种记忆形成背后的高分子守恒，加利福尼亚海陆软体动物具有简单的神经回路，为详细描述睡眠、生物钟和记忆之间的体内相互作用提供了理想的模型。之前，我们描述了短期、中期和长期记忆的操作性学习范式，即学习食物是不可食用的（LFI）。我们对澳大利亚人的睡眠进行了分析，发现澳大利亚人的睡眠模式与人类的睡眠模式相似，睡眠只发生在夜间的长时间巩固期。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。本提案的目标是确定睡眠剥夺引起的细胞变化和基因表达的变化，特别是在参与摄食行为和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，重要的是，为未来改善记忆和表现的治疗方法提供研究基础。

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.