Brain Plasticity and Local Sleep Homeostasis: A Clinical Perspective

睡眠功能的突触稳态假说的关键方面将在前三个项目中进行测试， 该中心的应用包括：i）清醒期间的大脑可塑性导致分子， 反映突触增强发生的电生理和代谢“痕迹”; ii）突触增强 反过来，增强作用负责随后睡眠期间更高水平的慢波;以及iii）睡眠 慢波对于学习后皮层回路的重新正常化和增强 睡眠后的表现。这个项目将在临床上测试突触稳态假说 重度抑郁症患者。大约一半的抑郁症患者表现出急性 对睡眠剥夺的抗抑郁反应。许多相同的突触增强的分子标记 抗抑郁药物也会引起睡眠剥夺，这表明睡眠 剥夺和抗抑郁药都通过诱导可塑性相关基因起作用。根据 假设，这些基因的激活应该与睡眠慢波的增加有关。目标1 研究证实，抑郁症患者可以分为慢波正常下降的患者， 活动（SWA）在夜间和那些谁不，并扩展我们的初步研究结果，抑郁症 也可以细分为那些谁显示正常与异常地形和局部稳态 SWA的规则。目标2将采用与项目II和III相同的视觉任务，以证明 具有异常SWA稳态的抑郁症患者亚组将表现出受损的局部稳态， 与SWA稳态更正常的亚组相比，睡眠依赖性学习减少。 最后，目标3将检验睡眠剥夺会产生抗抑郁药的假设预测 反应只有在抑郁症的主题与正常的时间进程和地形的SWA在夜间， SWA的活性对睡眠剥夺的稳态挑战的正常反应。

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.