Brain Plasticity and Local Sleep Homeostasis: A Clinical Perspective

大脑可塑性和局部睡眠稳态：临床视角

• 批准号: 8118165
• 负责人: RUTH M BENCA
• 金额: $ 18.57万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118165
• 关键词: Acute; Address; Affect; Antidepressive Agents; Area; Biological Preservation; Brain; Brain region; Brain-Derived Neurotrophic Factor; Characteristics; Chemosensitization; Chronic; Clinical; Depressed mood; Disease; Effectiveness; Electrodes; Environment; Exposure to; Genes; Hand; Homeostasis; Hour; Impairment; Individual; Lead; Learning; Lesion; Major Depressive Disorder; Measures; Mediating; Mental Depression; Metabolic; Modeling; Molecular; Moods; Neurobehavioral Manifestations; Outcome; Patients; Pattern; Performance; Pharmaceutical Preparations; Population; Prefrontal Cortex; Protocols documentation; REM Sleep; Recovery; Regulation; Relative (related person); Reporting; Rotation; Sleep; Sleep Deprivation; Sleep Stages; Slow-Wave Sleep; Structure; Subgroup; Synapses; Testing; Therapeutic; Therapeutic Intervention; Time; Wakefulness; Work; base; clinical Diagnosis; depressive symptoms; deprivation; insight; molecular marker; noradrenergic; novel; receptor; response; sleep abnormalities; sleep regulation; trait; visual motor

Key aspects of the synaptic homeostasis hypothesis of sleep function will be tested in the first 3 projects of this center application, including that: i) brain plasticity during wakefulness leads to molecular, electrophysiological and metabolic "traces" reflecting the occurrence of synaptic potentiation; ii) synaptic potentiation, in turn, is responsible for higher levels of slow waves during subsequent sleep; and iii) sleep slow waves are necessary for the renormalization of cortical circuits after learning and for the enhancement of performance after sleep. This project will test the synaptic homeostasis hypothesis in a clinical population¿subjects with major depressive disorder. About half of depressives show an acute antidepressant response to sleep deprivation. Many of the same molecular markers of synaptic potentiation that are induced by sleep deprivation are also induced by antidepressant drugs, suggesting that sleep deprivation and antidepressants both act by the induction of plasticity-related genes. According to the hypothesis, activation of such genes should be associated with increased sleep slow waves. Aim 1 of this study will confirm that depressives can be subdivided into those who show a normal decline of slow wave activity (SWA) across the night and those who do not, and extend our preliminary findings that depressives can also be subdivided into those who show normal vs. abnormal topography and local homeostatic regulation of SWA. Aim 2 will employ the same visuomotor task as Projects II and III to demonstrate that the subgroup of depressives with abnormal SWA homeostasis will show impaired local homeostasis and decreased sleep-dependent learning in comparison to the subgroup with more normal SWA homeostasis. Finally, Aim 3 will test the hypothesis' prediction that sleep deprivation will produce an antidepressant response only in depressed subjects with a normal time course and topography of SWA during the night, as well a normal SWA activity response to the homeostatic challenge of sleep deprivation.

睡眠功能的突触动态平衡假说的关键方面将在 这一中心应用包括：i)清醒时大脑的可塑性导致分子， 反映突触增强发生的电生理和代谢“痕迹”；II)突触 在随后的睡眠中，增强反过来又导致较高水平的慢波；以及iii)睡眠 慢波是学习后皮层环路重整化和增强所必需的。 睡眠后的表现。该项目将在临床上检验突触动态平衡假说 研究对象为重度抑郁障碍患者。大约一半的抑郁症患者表现出急性 睡眠剥夺后的抗抑郁反应。突触增强的许多相同的分子标记 由睡眠不足引起的睡眠障碍也由抗抑郁药物引起，这表明睡眠 剥夺和抗抑郁药都是通过诱导可塑性相关基因发挥作用的。根据 假设，这些基因的激活应该与睡眠慢波增加有关。目标1 研究将证实，抑郁症患者可以细分为表现出正常慢波下降的人 夜间活动(SWA)和那些没有活动的人，并扩大了我们的初步发现，即抑郁症 也可细分为显示正常与异常地形图和局部动态平衡的患者 对SWA的监管。目标2将采用与项目II和项目III相同的视觉运动任务，以证明 SWA稳态异常的抑郁症患者亚组将表现出局部稳态受损和 与SWA动态平衡更正常的亚组相比，睡眠依赖学习减少。 最后，目标3将验证假设的预测，即睡眠不足将产生一种抗抑郁药物 反应仅限于有正常时间进程和夜间SWA地形图的抑郁症受试者，因为 一个正常的SWA活动对睡眠不足所带来的平衡挑战的反应。