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.

睡眠功能的突触稳态假设的关键方面将在前3个项目中进行测试 该中心应用，包括：i）清醒期间的大脑可塑性导致分子， 电生理和代谢“痕迹”反映了突触潜力的发生； ii）突触 反过来，增强是导致随后睡眠期间较高的慢波水平。和iii）睡眠 慢波对于学习和增强后的皮质回路重新归一化是必需的 睡眠后的表现。该项目将在临床中测试突触体内稳态假设 人口是严重抑郁症的受试者。大约一半的抑郁症表现出急性 抗抑郁药对睡眠剥夺的反应。许多相同的突触电位分子标记 由抗抑郁药引起的睡眠剥夺引起的诱导的药物，表明睡眠 剥夺和抗抑郁药都通过诱导与塑性相关的基因作用。根据 假设，这种基因的激活应与睡眠慢波增加有关。目标1 研究将确认可以将抑郁剂细分为那些表现出慢波正常下降的人 整个夜晚的活动（SWA）和那些不进行的活动，并扩展了我们的初步发现 也可以细分为那些显示正常与异常地形和当地体内平衡的人 SWA的调节。 AIM 2将采用与II和III项目相同的视觉运动任务，以证明 异常SWA稳态的抑郁症亚组将显示出局部稳态受损，并且 与SWA稳态更为正常的亚组相比，开发了睡眠依赖性学习。 最后，AIM 3将检验假设的预测，即睡眠剥夺会产生抗抑郁药 只有在夜间有正常时间课程和SWA地形的被拒绝的受试者中的回应， 正常的SWA活动反应对睡眠剥夺的稳态挑战。