Locus coeruleus modulation of sleep-induced insight gain.

蓝斑调节睡眠引起的洞察力增益。

• 批准号: 10528107
• 负责人: Ciorana Roman Ortiz
• 金额: $ 6.02万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-31 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10528107
• 关键词: Address; Affect; Animals; Behavior; Cognitive; Electroencephalography; Event; Extracellular Structure; Fire - disasters; Goals; Grant; Hippocampus (Brain); Impairment; Knowledge; Learning; Medial; Mediating; Memory; Modeling; Neurons; Pathway interactions; Pattern; Pattern Recognition; Phase; Play; Prefrontal Cortex; Probability; Role; Sleep; Slow-Wave Sleep; Structure; Task Performances; Training; Update; Work; density; executive function; experimental study; extracellular; improved; in vivo; insight; locus ceruleus structure; memory consolidation; memory recall; neural circuit; non rapid eye movement; noradrenergic; novel therapeutics; optogenetics; sleep spindle; tool; trait

Abstract: The goal of this proposal is to elucidate how LC-NA promotes specific sleep features to directly facilitate insight gain. Sleep oscillations during NREM sleep have been identified that mediate memory updating and consolidation. LC noradrenergic neurons fire prior of slow waves, whereas LC becomes silent during spindle events all through NREM. A recent study from the Poe lab provided evidence that abnormal LC activity decreases sleep spindle density and affects memory consolidation. However, it is unclear how LC-NA activity gates sleep-dependent neural circuits to improve memory updating and temporal pattern recognition. Thus Aim 1 will use extracellular recordings, EGG/EMG and computational approaches to characterize LC noradrenergic activity patterns during sleep in animals that gain insight after a sleep period. Then in Aim 2 we will evaluate if LC noradrenergic activation or inhibition during sleep is essential to promote insight learning using optogenetic tools. Finally, in Aim 3 utilizing multi-structure extracellular recordings and optogenetic tools we will assess the effects of LC-NA projections to hippocampus (Hipp) and medial prefrontal cortex (mPFC). Taken together, the experiments to be performed in this proposal will provide valuable knowledge on how patterns of activity during sleep promote off-line mechanisms that allow for memory updating and provide novel therapeutic venues.

抽象的： 该提案的目的是阐明LC-NA如何促进特定的睡眠特征以直接促进洞察力增益。已经确定了NREM睡眠期间的睡眠振荡，可以介导记忆更新和整合。 LC去甲肾上腺素能神经元在慢波之前发射，而LC在整个NREM期间在主轴事件期间变得沉默。 POE实验室的最新研究提供了证据，表明异常LC活性会降低睡眠纺锤体密度并影响记忆巩固。但是，尚不清楚LC-NA活性门如何与睡眠依赖性神经回路改善记忆更新和时间模式识别。因此，AIM 1将使用细胞外记录，鸡蛋/EMG和计算方法来表征在睡眠期间睡眠中睡眠期间LC甲肾上腺素能活性模式的表征。然后，在AIM 2中，我们将评估LC去甲肾上腺素能激活或睡眠期间的抑制对于使用光遗传学工具促进洞察力学习至关重要。最后，在AIM 3中，利用多结构外记录和光遗传学工具，我们将评估LC-NA投影对海马（HIPP）（HIPP）和内侧前额叶皮层（MPFC）的影响。综上所述，在本提案中进行的实验将提供有关睡眠期间活动模式如何促进离线机制如何促进记忆更新并提供新型治疗场所的宝贵知识。