Cognitive Modulation of Circadian Rhythms

昼夜节律的认知调节

• 批准号: 7753241
• 负责人: THERESA M LEE
• 金额: $ 29.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-16 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7753241
• 关键词: Acetylcholine; Adrenal Glands; Adrenalectomy; Alzheimer' s Disease; Animals; Arousal; Attention; Behavioral; Bipolar Disorder; Body Temperature; Cholinergic Agonists; Circadian Rhythms; Cognition; Cognitive; Complex; Corticosterone; Cues; Data; Deafferentation procedure; Depressed mood; Deterioration; Development; Disease; Eating; Event; Exposure to; Goals; Immunotoxins; Injection of therapeutic agent; Learning; Lesion; Light; Masks; Measures; Medial; Mediating; Melatonin; Mental Depression; Midbrain structure; Neurobehavioral Manifestations; Neurons; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Photic Stimulation; Physiological; Prefrontal Cortex; Process; Rattus; Recovery; Reinforcement Schedule; Reporting; Research; Research Personnel; Resting Phase; Role; Running; Saline; Signal Transduction; Son; Stimulus; System; Testing; Time; Training; age related; basal forebrain; basal forebrain cholinergic neurons; biological adaptation to stress; cholinergic; cognitive function; hypothalamic-pituitary-adrenal axis; insight; noradrenergic; normal aging; programs; research study; response; shift work; stressor; suprachiasmatic nucleus; treatment duration

DESCRIPTION (provided by applicant): We recently observed that performance of a cognitive task (specifically an attention-demanding task, not involving stressors or unexpected events and not requiring noradrenergic activation), declined during recovery from a phase-shift of the light cycle. Furthermore, stable circadian activity patterns were radically altered by daily training on such a task during the subjective rest phase (i.e., rats became day active). As performance on this task depends upon the integrity and activity of the basal forebrain - cortical cholinergic input system, and as activity in this system during performance is controlled by top-down prefrontal regions, the main goal of the proposed research is to determine the neuronal mechanisms allowing cognition- associated cholinergic activity to modulate circadian rhythms. Although the HPA axis and central attention mechanisms interact, the impact of bottom-up and top-down arousal mechanisms on circadian rhythms appears to be quite different. We hypothesize that the effects of cognitive activity on circadian rhythms are mediated via activation of basal forebrain cholinergic projections to the SCN, while stimulation of the HPA axis contributes little to the reorganization of cognition-entrained rhythms. Specific Aim 1 tests the hypothesis that bottom-up, HPA-mediated arousal is not sufficient or necessary for entraining activity during the rest phase. We will test the hypothesis by examining changes in corticosterone release and ACh release following entrainment to a non-photic signal during the day, while intact or after adrenalectomy or basal forebrain lesions. Specific Aim 2 tests the hypothesis that the pattern of circadian re-organization caused by performance of an attention-demanding cognitive task is gradual, learning-related, and time-of-day specific. Specific Aim 3 tests the hypothesis that basal forebrain cholinergic efferents to the SCN are necessary for the effects of attention-demanding cognition on circadian entrainment. Results from these experiments may increase our understanding of circadian changes associated with shift work, Alzheimer's disease, depression and bipolar disorder. Potential treatments for such disorders may include manipulation of the cortical cholinergic system control of circadian entrainment.

描述（由申请人提供）：我们最近观察到，认知任务（特别是需要注意力的任务，不涉及压力源或意外事件，并且不需要去甲肾上腺素激活）的表现在从光周期相移恢复期间下降。此外，在主观休息阶段（即老鼠变得白天活跃），稳定的昼夜节律活动模式因此类任务的日常训练而发生根本性改变。由于这项任务的表现取决于基底前脑-皮质胆碱能输入系统的完整性和活动，并且该系统在表现过程中的活动是由自上而下的前额叶区域控制的，因此本研究的主要目标是确定允许认知相关胆碱能活动调节昼夜节律的神经元机制。尽管 HPA 轴和中央注意机制相互作用，但自下而上和自上而下的唤醒机制对昼夜节律的影响似乎有很大不同。我们假设认知活动对昼夜节律的影响是通过激活基底前脑胆碱能投射到 SCN 来介导的，而刺激 HPA 轴对认知节律的重组几乎没有贡献。具体目标 1 检验了以下假设：自下而上、HPA 介导的唤醒对于在休息阶段进行活动来说是不够或必要的。我们将通过检查白天非光信号夹带后皮质酮释放和乙酰胆碱释放的变化来检验该假设，同时完好无损或在肾上腺切除术或基底前脑病变后。具体目标 2 检验了以下假设：由执行需要注意力的认知任务引起的昼夜节律重组模式是渐进的、与学习相关的、并且是一天中特定时间的。具体目标 3 检验了以下假设：基底前脑胆碱能传出至 SCN 对于注意力需求认知对昼夜节律影响的影响是必要的。这些实验的结果可能会增加我们对与轮班工作、阿尔茨海默病、抑郁症和双相情感障碍相关的昼夜节律变化的理解。此类疾病的潜在治疗方法可能包括操纵皮质胆碱能系统控制昼夜节律。

项目成果

Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality, and performance.

• DOI: 10.1523/jneurosci.2271-12.2012
• 发表时间: 2012-08-29
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Paolone G;Lee TM;Sarter M
• 通讯作者: Sarter M