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（申请人提供）：了解如何调制学习和记忆是了解如何形成记忆的重要方面。神经系统的情绪状态，各种环境因素和疾病会影响记忆的形成。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。在解决这些目标时，我们发现昼夜节律调节了一种简单的长期记忆形式，对Aplysia中尾siphon撤回反射的长期敏化。白天对动物进行训练时会形成长期记忆，但在夜间接受训练时，记忆力少得多。但是，在白天和黑夜中，对相同行为的短期记忆形成也同样很好。该特定目的是通过调查其他形式的记忆的昼夜节律调节以及负责长期记忆调节的机制来扩展我们的先前研究。具体目的1是确定昼夜节律学习和记忆调制的范围和功能。我们将研究一种更复杂的学习形式的昼夜节律调节（学习食物是不可食用的），我们将研究昼夜夜间学习的昼夜节律调节。具体目的2是确定昼夜节律学习和记忆调制的电路。我们将研究昼夜节律起搏器在眼睛中的作用，我们将确定记忆的昼夜节律调节是否持续在半独立性的制备中。具体目的3是确定昼夜节律是否通过在学习和记忆电路中的促进性血清素能神经元调节来调节学习和记忆。我们将研究昼夜节律释放5-羟色胺的调制是否负责记忆形成的调节。具体目的4是确定在感觉神经元中诱导长期记忆所需的生化和分子事件，负责记忆的昼夜节律调节。我们将研究昼夜节律对APC/EBP mRNA合成的调制以及在记忆形成过程中MAPK和PKA的激活。除了阐明学习和记忆的调节外，这项研究还将提供有关昼夜节律如何调节其输出以产生节奏的见解。此外，了解模拟记忆形成的机制将有助于尝试改善记忆力以及治疗影响记忆的疾病。