Brain Plasticity and Local Sleep Homeostasis: A Molecular Perspective

大脑可塑性和局部睡眠稳态：分子视角

• 批准号: 8118162
• 负责人: Chiara Cirelli
• 金额: $ 19.8万
• 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/8118162
• 关键词: AMPA Receptors; Adult; Area; BDNF gene; Behavioral; Behavioral Paradigm; Biological Process; Brain; Brain region; Brain-Derived Neurotrophic Factor; Calcineurin; Calcium/calmodulin-dependent protein kinase; Cellular Membrane; Cerebral cortex; Chemosensitization; Circadian Rhythms; Contralateral; Data; Electrodes; Electroencephalogram; Endocytosis; Energy Metabolism; Environment; Event-Related Potentials; Excitatory Synapse; Exploratory Behavior; Exposure to; F-Actin; Forelimb; Frequencies; Gene Expression; Genes; GluR2 subunit AMPA receptor; Glutamates; Hand; Homeostasis; Hour; Human; Individual; Injection of therapeutic agent; Learning; Link; Long-Term Depression; Long-Term Potentiation; Measurement; Measures; Mediating; Memory; Mental Depression; Molecular; Motor; Motor Cortex; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; NR1 gene; Neurons; Occipital lobe; Parietal; Performance; Phosphorylation; Plastics; Preparation; Process; Protein Dephosphorylation; Proteins; Protocols documentation; Rattus; Relative (related person); Side; Site; Sleep; Sleep Deprivation; Slow-Wave Sleep; Surface; Synapses; Testing; Time; Toxin; Training; Wakefulness; Work; awake; brain electrical activity; calmodulin-dependent protein kinase II; gene induction; in vivo; molecular marker; motor learning; receptor; research study; response; synaptic depression

Slow wave activity (SWA; 0.5-4.0 Hz) in the sleep electroencephalogram is a marker of sleep need, increasing with the duration of prior wakefulness and decreasing exponentially during sleep. The biological process responsible for the increase of SWA as a function of prior wakefulness, however, remains unknown. According to a recent hypothesis - the synaptic homeostasis hypothesis of sleep function - plastic processes occurring during wakefulness result in a net increase in synaptic strength in many cortical circuits. As a consequence, when cortical neurons begin oscillating at low frequencies during sleep, they become strongly synchronized, leading to slow waves of high amplitude and thereby to increased SWA. These slow waves, in turn, are responsible for the renormalization of synaptic strength and have beneficial effects on energy metabolism and performance. Recent work has shown that, consistent with the hypothesis, wakefulness is associated with the induction of genes involved in synaptic potentiation, such as Arc, BDNF, P-CREB, and NGFI-A, while sleep is associated with higher expression of genes involved in synaptic depression, such as calcineurin and NSF. Building upon these results, this Project will examine specific molecular markers of synaptic potentiation/depression in parallel with local field potential recordings of SWA in freely behaving rats. Aim 1 will quantify synaptic AMPA receptor number and phosphorylation state in wakefulness and sleep to confirm the prediction that the former is associated with synaptic potentiation and the latter with synaptic depression. Aim 2 will test the prediction that sleep SWA will be higher, for the same amount of wakefulness, if markers of synaptic potentiation are induced at higher levels through increased exploratory activity. Aim 3 will employ a forelimb motor learning task inspired by the human learning task used in Projects II, III, and IV to test the prediction that local molecular changes associated with synaptic potentiation are associated with a local increase in SWA homeostasis in rat contralateral motor cortex. Thus, this Project will provide the molecular / electrophysiological underpinning for the entire proposal.

睡眠脑电图中的慢波活动（SWA; 0.5-4.0 Hz）是睡眠需求的标志。