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

基本信息

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
项目类别：
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

项目摘要

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）是睡眠需要的标志，随着先前清醒时间的延长而增加，并在睡眠期间呈指数下降。生物的然而，导致 SWA 作为先前清醒度函数增加的过程仍然未知。根据最近的假设 - 睡眠功能的突触稳态假说 - 可塑过程清醒期间发生的反应会导致许多皮质回路中突触强度的净增加。作为一个结果，当皮质神经元在睡眠期间开始低频振荡时，它们会变得强烈同步，导致高振幅的慢波，从而增加 SWA。这些慢波，在转，负责突触强度的重新正常化并对能量产生有益的影响新陈代谢和性能。最近的研究表明，与假设一致，觉醒是与突触增强相关基因的诱导相关，例如 Arc、BDNF、P-CREB 和 NGFI-A，而睡眠与突触抑制相关基因的较高表达有关，例如钙调神经磷酸酶和 NSF。基于这些结果，该项目将检查特定的分子标记突触增强/抑制与自由行为时 SWA 的局部场电位记录并行老鼠。目标 1 将量化清醒和睡眠状态下的突触 AMPA 受体数量和磷酸化状态证实前者与突触增强有关而后者与突触增强有关的预测沮丧。目标 2 将测试在清醒时间相同的情况下睡眠 SWA 会更高的预测，如果通过增加探索活动来诱导更高水平的突触增强标记。目标 3 将采用受项目 II、III 和 IV 中使用的人类学习任务启发的前肢运动学习任务测试与突触增强相关的局部分子变化与大鼠对侧运动皮层 SWA 稳态的局部增加。因此，该项目将提供整个提案的分子/电生理学基础。