Role of cortical interneurons in synchronization of brain electroencephalogram

皮质中间神经元在脑电图同步中的作用

基本信息

批准号：
7886106
负责人：
DMITRY GERASHCHENKO
金额：
$ 27.77万
依托单位：
HARVARD MEDICAL SCHOOL
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：
2010-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7886106
关键词：
Ablation Affect Afferent Neurons Alcohol or Other Drugs use Animals Area Brain Brain Part Brain region Cells Cerebral cortex Circadian Rhythms Corpus striatum structure DNA Data Diphtheria Toxin Distant Dose Electroencephalogram Electron Microscopy Environment Enzyme Inhibitor Drugs Enzyme Inhibitors Exhibits Frequencies Functional disorder Generations Genes Glutamate Decarboxylase Hippocampus (Brain)Histidine Decarboxylase Homeostasis Interneurons Knockout Mice Label Laboratory Finding Lead Lesion Light Measures Mediating Mental disorders Motor Activity Mus NG-Nitroarginine Methyl Ester Neurologic Neurons Neurotransmitters Nitric Oxide Nitric Oxide Synthase Type I Open Reading Frames Pharmaceutical Preparations Phase Phenotype Procedures Production Property Protein Isoforms Protocols documentation Rattus Recovery Regulation Research Role Running Secondary to Sensory Side Site Sleep Sleep Deprivation Sleep Disorders Slow-Wave Sleep Somatosensory Cortex Specificity Staining method Stains Subfamily lentivirinae Testing Time Tracer Tumor Necrosis Factor-alpha Tyrosine 3-Monooxygenase Varicosity Vibrissae Wild Type Mouse Work arginine methyl ester awake base circadian pacemaker hippocampal pyramidal neuron human TNF protein inhibitor/antagonist neuropeptide Y non rapid eye movement novel strategies promoter public health relevance research study response substance P-saporin suprachiasmatic nucleus

项目摘要

DESCRIPTION (provided by applicant): Synchronization of neuronal activity within and across brain regions is a fundamental property of cortical and subcortical networks needed for normal brain functions. Synchronization of electroencephalogram (EEG) in the frequency range of 1-4 Hz, referred to as slow wave activity (SWA), is observed during slow wave sleep and is thought to be essential for the recuperative function of sleep. Recent work in our laboratory found that changes in SWA parallel the changes in the activity of neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the cortex in three mammalian species. These results suggest that nNOS neurons in the cortex are part of the brain circuit that is involved in the generation of SWA. Since SWA is an established marker of the homeostatic sleep drive, the nNOS neuronal circuit is expected to be activated by homeostatic mechanisms. The proposed studies will test the following hypotheses: (1) changes in the activity of nNOS cells in the cortex correlate with SWA, (2) changes in the activity of nNOS cells in the cortex are independent of circadian input from the suprachiasmatic nucleus, (3) anatomical properties of nNOS cells are consistent with the role of these neurons in EEG synchronization, (4) nitric oxide production by nNOS is involved in SWA generation, and (5) selective ablation of nNOS cells leads to disturbances in SWA production and sleep homeostasis. This research will be a first step in characterizing newly discovered sleep-active neurons in the cortex. It will provide important information about regulation of brain activity by nNOS neurons and may advance our understanding not only of the pathophysiology of sleep disorders, but also of neurological and psychiatric diseases that involve the cerebral cortex. PUBLIC HEALTH RELEVANCE: Research on the role of sleep-active neurons recently discovered in the cerebral cortex will provide new information about regulation of brain activity. An understanding of the functions and mechanisms of these neurons may lead to new approaches for treating a variety of neurological and psychiatric diseases involving the cerebral cortex, as well as for ameliorating common sleep disorders.

描述（由申请人提供）：大脑区域内和跨大脑区域内神经元活动的同步是正常脑功能所需的皮质和皮质下网络的基本特性。在慢波睡眠期间观察到脑电脑图（EEG）在1-4 Hz的频率范围内（称为慢波活动（SWA））的同步，被认为对于睡眠的恢复功能至关重要。我们实验室的最新工作发现，SWA的变化与三种哺乳动物物种的皮质中神经元一氧化氮合酶（NNOS） - 免疫反应细胞的活性变化。这些结果表明，皮质中的NNO神经元是SWA产生的脑电路的一部分。由于SWA是稳态睡眠驱动器的既定标记，因此NNOS神经元电路有望通过稳态机制激活。 The proposed studies will test the following hypotheses: (1) changes in the activity of nNOS cells in the cortex correlate with SWA, (2) changes in the activity of nNOS cells in the cortex are independent of circadian input from the suprachiasmatic nucleus, (3) anatomical properties of nNOS cells are consistent with the role of these neurons in EEG synchronization, (4) nitric oxide production by NNOS参与了SWA的生成，（5）NNOS细胞的选择性消融会导致SWA产生和睡眠稳态的干扰。这项研究将是表征皮质中新发现的睡眠神经元的第一步。它将提供有关NNOS神经元调节大脑活动的重要信息，并不仅可以提高我们对睡眠障碍的病理生理学的理解，而且还可以对涉及大脑皮质的神经和精神病疾病的理解。公共卫生相关性：关于最近在大脑皮层中发现的睡眠活动神经元作用的研究将提供有关调节大脑活动的新信息。对这些神经元功能和机制的理解可能会导致新的方法来治疗涉及大脑皮质的各种神经和精神病，以及改善常见的睡眠障碍。