Metabolic and Dietary Influences on Striatal Contributions to Taste-motivated Behavior

摘要： 这项建议的目的是阐明LC-NA如何促进特定的睡眠特征，以直接促进洞察力的获得。NREM睡眠期间的睡眠振荡已被确定为调节记忆更新和巩固。LC去甲肾上腺素能神经元先于慢波放电，而LC在整个NREM的纺锤波事件中变得沉默。PoE实验室最近的一项研究提供了证据，表明LC活动异常会降低睡眠纺锤体密度，并影响记忆巩固。然而，目前尚不清楚LC-NA活动如何通过调节睡眠相关神经回路来改善记忆更新和时间模式识别。因此，目标1将使用细胞外记录、EGG/EMG和计算方法来表征动物在睡眠期间的LC去甲肾上腺素能活动模式，这些动物在睡眠后获得洞察力。然后，在目标2中，我们将评估LC去甲肾上腺素能在睡眠中的激活或抑制是否对使用光遗传工具促进洞察学习至关重要。最后，在目标3中，利用多结构细胞外记录和光遗传学工具，我们将评估LC-NA投射到海马区(HIPP)和内侧前额叶皮质(MPFC)的影响。综上所述，这项提案中将要进行的实验将提供关于睡眠中的活动模式如何促进允许记忆更新的离线机制的宝贵知识，并提供新的治疗场所。

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.