Circadian Modulation of Long-term Memory Formation

长期记忆形成的昼夜节律调节

• 批准号: 6946333
• 负责人: ARNOLD none ESKIN
• 金额: $ 30.91万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946333
• 关键词: Aplysia; association learning; behavior test; behavioral /social science research tag; biological clocks; circadian rhythms; enzyme activity; eye; forskolin; gene expression; long term memory; messenger RNA; mitogen activated protein kinase; neurons; neuroregulation; neurotransmitter transport; phosphorylation; protein kinase A; serotonin

DESCRIPTION (provided by applicant): Understanding how learning and memory are modulated is an important aspect of understanding how memories are formed. Emotional state, various environmental factors, and diseases of the nervous system can impact the formation of memory. The long-term goals of our research are to define factors that normally modulate memory formation and to determine how these factors modulate learning and memory. In addressing these goals, we discovered that the circadian clock modulates a simple form of long-term memory, long-term sensitization of the tail-siphon withdrawal reflex in Aplysia. Animals form long-term memory when they are trained during the day but form much less memory when they are trained at night. However, short-term memory of the same behavior is formed equally well during the day and night. The Specific Aims extend our previous research by investigating circadian modulation of other forms of memory and the mechanisms responsible for circadian modulation of long-term memory. Specific Aim 1 is to determine the scope and function of circadian modulation of learning and memory. We will investigate circadian modulation of a more complex associative form of learning (learning that food is inedible), and we will investigate circadian modulation of learning in nocturnal species of Aplysia. Specific Aim 2 is to determine the circuitry involved in the circadian modulation of learning and memory. We will investigate the role of the circadian pacemaker in the eye, and we will determine whether circadian modulation of memory persists in a semi-intact preparation. Specific Aim 3 is to determine whether the circadian clock modulates learning and memory through modulation of facilitatory serotonergic neurons in the learning and memory circuitry. We will investigate whether circadian modulation of release of serotonin is responsible for the modulation of memory formation. Specific Aim 4 is to determine which biochemical and molecular events necessary for the induction of long-term memory in sensory neurons are responsible for the circadian modulation of memory. We will investigate circadian modulation of synthesis of ApC/EBP mRNA and activation of MAPK and PKA during the formation of memory. In addition to elucidating the modulation of learning and memory, this research will provide insights into how the circadian clock regulates its outputs to produce rhythms. Furthermore, knowing the mechanisms by which memory formation is modulated will aid attempts to improve memory as well as to treat diseases that affect memory.

描述（由申请人提供）：了解学习和记忆如何调节是了解记忆如何形成的一个重要方面。情绪状态、各种环境因素以及神经系统疾病都会影响记忆的形成。我们研究的长期目标是定义通常调节记忆形成的因素，并确定这些因素如何调节学习和记忆。在实现这些目标的过程中，我们发现生物钟调节一种简单形式的长期记忆，即海兔尾虹吸撤回反射的长期敏化。动物在白天训练时会形成长期记忆，但在夜间训练时形成的记忆要少得多。然而，同一行为的短期记忆在白天和晚上形成得同样好。具体目标通过研究其他形式的记忆的昼夜节律调节以及负责长期记忆的昼夜节律调节的机制来扩展我们之前的研究。具体目标1是确定学习和记忆的昼夜节律调节的范围和功能。我们将研究更复杂的联想学习形式（学习食物不可食用）的昼夜节律调节，并且我们将研究海兔夜间活动物种学习的昼夜节律调节。具体目标 2 是确定参与学习和记忆昼夜节律调节的电路。我们将研究昼夜节律起搏器在眼睛中的作用，并将确定记忆的昼夜节律调节是否在半完整的制剂中持续存在。具体目标 3 是确定生物钟是否通过调节学习和记忆回路中的促进性血清素能神经元来调节学习和记忆。我们将研究血清素释放的昼夜节律调节是否负责记忆形成的调节。具体目标 4 是确定感觉神经元中诱导长期记忆所需的哪些生化和分子事件负责记忆的昼夜节律调节。我们将研究记忆形成过程中 ApC/EBP mRNA 合成以及 MAPK 和 PKA 激活的昼夜节律调节。除了阐明学习和记忆的调节之外，这项研究还将深入了解生物钟如何调节其输出以产生节律。此外，了解调节记忆形成的机制将有助于改善记忆以及治疗影响记忆的疾病。