Brain Plasticity and Local Sleep Homeostasis: A Metabolic Perspective

正电子发射断层扫描和功能磁共振脑功能成像 成像(FMRI)为人类大脑的功能提供了独特的新见解。大脑发出的信号 这些成像设备检测到的结果是局部脑循环和能量变化的结果 新陈代谢提供了一个独特的机会，迄今尚未探索，以检查突触功能 本申请中提出的突触内稳态假说的背景。成像的两个特征 在这方面，信号特别重要。第一，基于循环和代谢变化的成像 与大脑功能相关的基因对突触活动的变化特别敏感。这反映了这样一个事实 树突和轴突终末的表面积与体积之比很高，使得突触的新陈代谢活动非常活跃。 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。 代谢活性，并在成像信号中唯一识别，这是由于使用有氧糖酵解 星形胶质细胞将其从突触中移除。因为谷氨酸已经被明确地鉴定为具有 在学习和记忆中扮演着重要的角色，这种有趣的因素组合使大脑成像与PET 和功能磁共振成像在一个独特的位置来测试突触稳态假说的重要方面。在 建议的实验我们将同时使用PET和FMRI以及EEC。我们假设学习将会 与静息状态下大脑有氧糖酵解持续的、区域性的增加有关 (清醒，闭着眼睛静静地躺着)，这不仅表现为葡萄糖代谢的增加 这比用PET测量的耗氧量的任何增加都要大，但也是在 FMRI BOLD信号的自发波动，是内在活动和 大脑的组织。此外，我们预测这些学习引起的变化将回到基线 在一晚正常睡眠后，但如果选择性地扰乱SWS，则不会这样做。我们相信这些都是 实验将提供与我们理解突触内稳态相关的关键新信息 假设。值得注意的是，这项研究是在一种新的和 具有高度互补性的人才和兴趣的调查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。

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.