Signaling and Circadian Modulation Regulating Associative Memory in Aplysia

海兔联想记忆的信号传导和昼夜节律调节

• 批准号: 7677424
• 负责人: Lisa Carlson Lyons
• 金额: $ 27.54万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677424
• 关键词: Address; Affect; Age; Animals; Aplysia; Behavior; Behavioral; Biochemical; Biological Assay; CCAAT-Enhancer-Binding Proteins; Circadian Rhythms; Cyclic AMP-Dependent Protein Kinases; Educational Status; Event; Food; Future; Genetic Transcription; Goals; Health; Learning; MAPK14 gene; Marines; Memory; Methods; Molecular; Motivation; Nature; Output; Pathway interactions; Performance; Phosphoric Monoester Hydrolases; Phosphotransferases; Physiological; Process; Regulation; Regulatory Element; Research; Role; Short-Term Memory; Signal Pathway; Signal Transduction; Stress; Testing; Therapeutic; Time; Training; Transcriptional Activation; Translations; base; circadian pacemaker; classical conditioning; computerized data processing; factor C; improved; long term memory; memory process; research study; transcription factor

DESCRIPTION (provided by applicant): To fully understand learning and the formation of memory, it is necessary to understand both the basic mechanisms responsible for the induction and consolidation of memory, as well as the processes responsible for the modulation of those basic processes. Many factors modulate the processes of memory formation including general health, stress, motivation, age and the time of day. The long-term objectives of our research are to understand the modulation of long-term associative memory formation by the circadian clock including the underlying molecular mechanisms, the physiological function and the behavioral consequences. The circadian clock regulates long-term memory formation in Aplysia californica, such that animals form robust long-term memory when trained during the day, but no long-term memory when trained at night. We will investigate the signaling pathways involved in an operant, associative form of learning in Aplysia, learning that food is inedible (LFI), and modulation by the circadian clock using behavioral, pharmacological and biochemical assays. In Specific Aim 1, we will identify the kinase signaling pathways necessary for LFI and determine whether the activation of these kinases is modulated by the circadian clock. Specifically, we will determine whether PKG, MARK and PKA signaling are necessary for LFI. The goal of Aim 2 is to determine whether the circadian clock modulates learning-induced transcription for LFI memory and whether the transcription factor ApC/EBP is involved in LFI. Specific Aim 3 examines the effect, at the molecular level, of training animals at night when they only form short-term memories and investigates methods of converting the partial memory into long-term memory. In Aim 4, we examine negative regulatory elements in long-term memory formation. We will investigate whether the circadian clock regulates p38 kinase activity or phosphatase activity. This research will significantly contribute to our understanding of the molecular mechanisms underlying associative operant learning in Aplysia as well as greatly furthering our understanding of the regulation of output behaviors by the circadian clock. One objective of the proposed experiments is to determine how circadian suppression of long-term memory formation at night may be relieved to improve memory formation at night. Thus, this research will provide a basis of research for future therapeutic treatments to improve memory and performance.

描述（由申请人提供）：为了充分理解学习和记忆的形成，有必要了解负责记忆诱导和巩固的基本机制，以及负责调制这些基本过程的过程。许多因素调节记忆形成的过程，包括一般健康，压力，动机，年龄和一天中的时间。我们研究的长期目标是了解昼夜节律的长期关联记忆形成的调节，包括潜在的分子机制，生理功能和行为后果。昼夜节律的时钟调节了加利福尼亚州阿普利西亚的长期记忆形成，使动物在白天接受训练时会形成强大的长期记忆，但在夜间接受训练时没有长期记忆。我们将研究Aplysia中学习的操作，关联形式的信号通路，了解食物是不可食用的（LFI），并使用行为，药理和生化测定法进行了昼夜节律的调节。在特定目标1中，我们将确定LFI所需的激酶信号通路，并确定这些激酶的激活是否由昼夜节律调节。具体而言，我们将确定LFI是否需要PKG，MARK和PKA信号传导。 AIM 2的目的是确定昼夜节律时钟是否调节学习诱导的LFI记忆的转录以及转录因子APC/EBP是否参与LFI。特定目标3检查了夜间训练动物的影响，当它们仅形成短期记忆并研究将部分记忆转化为长期记忆的方法。在AIM 4中，我们检查了长期记忆形成中的负调节元素。我们将调查昼夜节律调节P38激酶活性还是磷酸酶活性。这项研究将极大地有助于我们理解Aplysia中关联性操作学习的分子机制，并大大进一步发展了我们对昼夜节律时钟对输出行为调节的理解。提出的实验的一个目的是确定如何缓解昼夜节律抑制长期记忆形成，以改善夜间的记忆形成。因此，这项研究将为未来的治疗疗法提供研究，以改善记忆力和性能。