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: 7908798
• 负责人: Lisa Carlson Lyons
• 金额: $ 27.48万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908798
• 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的诱导和巩固的基本机制，以及负责调节这些基本过程的过程。许多因素调节记忆形成的过程，包括一般健康状况，压力，动机，年龄和一天中的时间。本研究的长期目标是了解生物钟对长时联想记忆形成的调节，包括其潜在的分子机制、生理功能和行为后果。昼夜节律钟调节着加州龙蜥的长期记忆形成，使得动物在白天训练时形成强大的长期记忆，但在夜间训练时没有长期记忆。我们将调查参与的信号通路的操作性，联想形式的学习在Aesthesia，学习，食物是不可食用的（LFI），和调制的昼夜节律钟使用行为，药理学和生化测定。在具体目标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受昼夜节律钟的调节。具体来说，我们将确定PKG，MARK和PKA信号是否是LFI所必需的。目的2的目标是确定生物钟是否调节LFI记忆的学习诱导的转录，以及转录因子ApC/EBP是否参与LFI。具体目标3在分子水平上考察了在夜间训练动物时，它们只形成短期记忆的效果，并研究了将部分记忆转化为长期记忆的方法。在目标4中，我们研究了长期记忆形成中的负调控元件。我们将研究生物钟是否调节p38激酶活性或磷酸酶活性。这项研究将有助于我们理解记忆缺失症的联想操作性学习的分子机制，并大大加深我们对生物钟调节输出行为的理解。所提出的实验的一个目的是确定如何在夜间解除长期记忆形成的昼夜节律抑制以改善夜间记忆形成。因此，本研究将为未来改善记忆和表现的治疗方法提供研究基础。

项目成果

Cycling behavior and memory formation.

• DOI: 10.1523/jneurosci.3353-09.2009
• 发表时间: 2009-10-14
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Gerstner JR;Lyons LC;Wright KP Jr;Loh DH;Rawashdeh O;Eckel-Mahan KL;Roman GW
• 通讯作者: Roman GW

Protein phosphatase-dependent circadian regulation of intermediate-term associative memory.

• DOI: 10.1523/jneurosci.4534-12.2013
• 发表时间: 2013-03-06
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Michel M;Gardner JS;Green CL;Organ CL;Lyons LC
• 通讯作者: Lyons LC

A brief retraining regulates the persistence and lability of a long-term memory.

短暂的再训练可以调节长期记忆的持久性和不稳定性。

• DOI: 10.1101/lm.1820010
• 发表时间: 2010
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Levitan,David;Twitto,Rachel;Levy,Roi;Lyons,LisaC;Susswein,AbrahamJ
• 通讯作者: Susswein,AbrahamJ

Characterization of sleep in Aplysia californica.

• DOI: 10.5665/sleep.3992
• 发表时间: 2014-09
• 期刊: Sleep
• 影响因子: 5.6
• 作者: A. Vorster;Harini C. Krishnan;C. Cirelli;Lisa C. Lyons

Role of proteasome-dependent protein degradation in long-term operant memory in Aplysia.

蛋白酶体依赖性蛋白质降解在海兔长期操作记忆中的作用。

• DOI: 10.1101/lm.043794.116
• 发表时间: 2017
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Lyons,LisaC;Gardner,JacobS;Gandour,CatherineE;Krishnan,HariniC
• 通讯作者: Krishnan,HariniC