Brain Plasticity and Local Sleep Homeostasis: A Metabolic Perspective

大脑可塑性和局部睡眠稳态：代谢视角

• 批准号: 7346832
• 负责人: MARCUS E RAICHLE
• 金额: $ 26.55万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7346832
• 关键词: Accounting; Aerobic; Anatomy; Area; Astrocytes; Belief; Blood Volume; Blood flow; Brain; Brain imaging; Chromosome Pairing; Collaborations; Data; Dendrites; Electroencephalography; Energy Metabolism; Exhibits; Eye; Functional Magnetic Resonance Imaging; Glucose; Glutamates; Homeostasis; Human; Image; Imaging Device; Imaging Techniques; Individual; Learning; Link; Localized; Magnetic Resonance Imaging; Measurement; Measures; Memory; Metabolic; Metabolism; Nature; Neuropil; Oxygen; Oxygen Consumption; Positioning Attribute; Positron-Emission Tomography; Presynaptic Terminals; Regional Blood Flow; Research; Research Personnel; Rest; Role; Rotation; Signal Transduction; Sleep; Sleep Deprivation; Slow-Wave Sleep; Surface; Synapses; Talents; Techniques; Testing; Wakefulness; Work; aerobic glycolysis; awake; base; brain circulation; brain metabolism; glucose metabolism; hemodynamics; insight; interest; memory process; neurotransmission; prevent; programs; research study; synaptic function

Functional brain imaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has provided unique new insights into the functioning of the human brain. The brain signals detected by these imaging devices result from a combination of changes in local brain circulation and energy metabolism that offer a unique opportunity, heretofore unexplored, to examine synaptic function in the context of the synaptic homeostasis hypothesis proposed in this application. Two features of the imaging signals are particularly important in this regard. First, imaging based on circulatory and metabolic changes associated with brain function is singularly sensitive to changes in synaptic activity. This reflects the fact that dendrites and axon terminals have high surface-to-volume ratios making synaptic activity metabolically very demanding. Second, glutamatergic neurotransmission appears to account for a very large fraction of this metabolic activity and is uniquely identified in imaging signals due to the use of aerobic glycolysis by astrocytes to remove it from synapses. Because glutamate has been specifically identified as having an important role in learning and memory, this interesting combination of factors places brain imaging with PET and fMRI in a unique position to test important aspects of the synaptic homeostasis hypothesis. In the proposed experiments we will utilize both PET and fMRI along with EEC. We hypothesize that learning will be associated with persistent, regionally specific increases in brain aerobic glycolysis in the resting state (awake, lying quietly with eyes closed) which will be manifest not only as an increase in glucose metabolism that is greater than any increase in oxygen consumption as measured with PET but also in an increase in the spontaneous fluctuations in the fMRI BOLD signal, an important indicator of the intrinsic activity and organization of the brain. Further, we predict that these learning induced changes.will return to baseline following a night of normal sleep but will not do so if SWS is selectively disrupted. We believe that these experiments will provide critical new information relevant to our understanding of the synaptic homeostasis hypothesis. It is important to note that this research is proposed to take place in the context of a new and important collaboration among investigators with highly complementary talents and interests. This is a unique opportunity for all concerned.

使用正电子发射断层扫描 (PET) 和功能磁共振进行功能性脑成像 成像（fMRI）为人类大脑的功能提供了独特的新见解。大脑发出信号 这些成像设备检测到的结果是局部大脑循环和能量变化的综合结果 新陈代谢提供了一个迄今为止尚未探索过的独特机会来检查突触功能 本申请中提出的突触稳态假说的背景。成像的两个特点 信号在这方面尤其重要。一、基于循环和代谢变化的成像 与大脑功能相关的神经元对突触活动的变化特别敏感。这反映了这样一个事实 树突和轴突末端具有较高的表面积与体积比，使得突触活动的代谢非常活跃 要求很高。其次，谷氨酸能神经传递似乎占其中的很大一部分。 代谢活动，并且由于使用有氧糖酵解而在成像信号中被独特地识别 星形胶质细胞将其从突触中移除。因为谷氨酸已被明确鉴定为具有 在学习和记忆中发挥着重要作用，这种有趣的因素组合使得 PET 脑成像成为可能 功能磁共振成像在测试突触稳态假说的重要方面具有独特的地位。在 在提议的实验中，我们将同时使用 PET 和 fMRI 以及 EEC。我们假设学习会 与静息状态下大脑有氧糖酵解持续、区域特异性增加有关 （醒着，闭着眼睛安静地躺着）这不仅会表现为葡萄糖代谢的增加 这不仅大于 PET 测量的耗氧量的增加，而且还大于 fMRI BOLD 信号的自发波动是内在活性的重要指标 大脑的组织。此外，我们预测这些学习引起的变化将恢复到基线 经过一晚的正常睡眠后，但如果 SWS 被选择性破坏，则不会这样做。我们相信，这些 实验将为我们理解突触稳态提供重要的新信息 假设。值得注意的是，这项研究是在一个新的背景下进行的。 具有高度互补才能和兴趣的研究人员之间的重要合作。这是一个 对所有相关人员来说都是独一无二的机会。