Neuronal Activity in Sleep & Wake in Alzheimer's Disease Mice

睡眠中的神经元活动

• 批准号: 10723302
• 负责人: Priyattam J. Shiromani
• 金额: $ 15.75万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723302
• 关键词: Acetylcholine; Alzheimer' s Disease; Alzheimer' s disease model; Animal Model; Area; Arousal; Behavior; Binding; Brain; Brain Diseases; Brain imaging; Budgets; Calcium; Cells; Color; Cre driver; Data; Disease; Disease Progression; Disease model; Dopamine; Female; Fluorescence; Funding; Goals; Histamine; Hypothalamic structure; Image; Lateral; Methods; Monitor; Mus; Neurons; Neurosciences; Norepinephrine; Pattern; Phenotype; Population; Positioning Attribute; REM Sleep; Research Personnel; Serotonin; Sleep; Sleep Deprivation; Sleep disturbances; Technical Expertise; Testing; Time; awake; brain cell; calcium indicator; design; falls; gamma-Aminobutyric Acid; hypocretin; imaging approach; male; microendoscopy; mouse model; network models; neural; neuronal patterning; new technology; non rapid eye movement; promoter; redshift; response; sensor; virtual; zona incerta

The deep-brain imaging approach (microendoscopy) is a high throughput method that identifies the temporal and spatial pattern of activity in specific phenotypes of neurons. We have hypothesized that activity in small networks can identify normal versus diseased brains. To test this hypothesis, we will use the two-wavelength miniscope to image activity of a subset of neurons in 5xFAD mice, a validated animal model of Alzheimer’s disease (normal versus the homozygous littermates). We have created promoter- driven calcium sensor that drives the red-shifted calcium indicator, jRGECO, into orexin-arousal neurons. A separate calcium sensor (GCaMP6m) in GABA sleep neurons will be used as comparison. The advantage of imaging neurons with two different wavelengths is that it allows for comparison of arousal versus sleep neurons as the brain transitions between wake and sleep. We will image activity of neurons that contain jRGECO and GCaMP during normal wake-sleep bouts and after 6h sleep loss. We hypothesize that there is an abnormal temporal pattern of fluorescence during the transition from wake to sleep in the brains of 5xFAD mice, and it worsens with progression of disease. This may explain the cause of the disrupted sleep-wake patterns in Alzheimer’s disease. We hypothesize that abnormal activity in deep brain circuits regulating sleep is a harbinger of disease. The overall impact of this small budget project is that it will identify activity of two different juxtapositioned neurons during wake, NREM and REM sleep in wildtype versus a disease model, which will aid in understanding how small clusters of neurons behave as the waking brain falls asleep.

深脑成像方法（微内核镜检查）是一种识别的高吞吐量方法 神经元特定表型中活性的暂时和空间模式。我们假设 小型网络中的活动可以识别正常的大脑与患病的大脑。为了检验这一假设，我们将使用 5xfad小鼠中神经元子集的图像活性的两波长的米科毛 阿尔茨海默氏病的模型（正常与纯合窝窝）。我们创建了启动子 - 驱动的钙传感器将红移钙指示剂JRGECO驱动到Orexin-arousal 神经元。 GABA睡眠神经元中的单独的钙传感器（GCAMP6M）将用作比较。 具有两个不同波长的成像神经元的优势在于，它允许比较 随着唤醒和睡眠之间的大脑过渡，唤醒与睡眠神经元与睡眠神经元。我们将图像活动的活动 在正常的唤醒时弹奏和6h睡眠后，含有JRGECO和GCAMP的神经元。我们 假设从唤醒过渡期间存在异常的临时荧光模式 在5xfad小鼠的大脑中睡觉，并且随着疾病的发展而恶化。这可以解释 阿尔茨海默氏病的睡眠觉醒模式中断的原因。我们假设异常活动 在深脑电路中，调节睡眠是疾病的预兆。这个小预算的总体影响 项目是，它将在唤醒，NREM和 REM在Wildtype与疾病模型中睡觉，这将有助于了解小簇 神经元在醒来的大脑睡着时的行为。