From Sleep to attention in Drosophila: Coordinating Brain Regions

果蝇从睡眠到注意力：协调大脑区域

• 批准号: 8118436
• 负责人: RALPH J GREENSPAN
• 金额: $ 29.08万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118436
• 关键词: Address; Affect; Arousal; Attention; Autistic Disorder; Behavioral; Brain; Brain Diseases; Brain Part; Brain region; Commissure; Coupling; Defect; Disease; Dopamine; Drosophila genus; Electrodes; Epidermal Growth Factor Receptor; Frequencies; Genetic; Glass; Goals; Impairment; Mammals; Maps; Measurable; Measures; Mediating; Microelectrodes; Modeling; Molecular; Phenotype; Physiological; Process; Regulation; Role; Schizophrenia; Signal Transduction Pathway; Site; Sleep; Synapses; System; Testing; Time; Transgenes; fly; genetic variant; public health relevance

DESCRIPTION (provided by applicant): Temporal coordination has been proposed as a fundamental underlying mechanism of attention in the mammalian brain and disturbances in temporal coordination are found in many brain disorders, including autism and schizophrenia, where they are potentially central to the defects. We have developed models for sleep and attention in the fruit fly Drosophila, and found that arousal levels in the fly brain are associated with different levels of temporal coordination (coherence). This proposal tests the idea that arousal states in the Drosophila brain, from sleep to attention, are brain-wide processes mediated by the degree and combinations of physiological coupling or linkage. This is measurable electrophysiologically as the level of temporal coordination (coherence) between various regions of the brain, being lowest in sleep and highest in attention-like states. Furthermore, we use genetic variants to test the idea that two highly conserved systems that control and modulate arousal at the molecular level in mammals and flies (dopamine and the EGFR signal transduction pathway) do so by their action on coherence. Finally, we test whether direct, local perturbations of coherence with hypo- or hyper-exciting transgenes alter arousal states. Thus, the goal is to integrate the molecular, physiological, and behavioral levels in an effort to understand the role and regulation of temporal coordination in producing different brain states. Specific Aims 1. Temporal coordination across the brain from sleep to attention: How much of the brain participates? Which regions? Are they the same for sleep and attention? 2. What effect do the known arousal systems in Drosophila have on attention and on temporal coordination? 3. How do genetic perturbations of temporal coordination, asymmetrically and by manipulation of commissures, alter arousal states? PUBLIC HEALTH RELEVANCE: Disturbances of timing in the brain are a shared and potentially critical feature of many brain disorders, including autism and schizophrenia. Our ability to address the impairments associated with these disorders would therefore benefit from a better understanding of the role of timing between different parts of the brain and the mechanisms that regulate it.

描述（由申请人提供）：时间协调已被认为是哺乳动物大脑中注意力的基本机制，并且在许多大脑疾病中都发现了时间协调的紊乱，包括自闭症和精神分裂症，它们可能是这些缺陷的核心。 我们开发了果蝇的睡眠和注意力模型，并发现果蝇大脑的唤醒水平与不同水平的时间协调（连贯性）相关。该提议测试了果蝇大脑中从睡眠到注意力的唤醒状态是由生理耦合或联系的程度和组合介导的全脑过程的观点。 这可以通过电生理学来测量，即大脑不同区域之间的时间协调（一致性）水平，在睡眠状态下最低，在注意力状态下最高。 此外，我们使用遗传变异来测试这样的想法：在哺乳动物和果蝇的分子水平上控制和调节唤醒的两个高度保守的系统（多巴胺和 EGFR 信号转导通路）通过其对一致性的作用来实现这一点。 最后，我们测试低兴奋或高兴奋转基因的直接局部一致性扰动是否会改变觉醒状态。 因此，我们的目标是整合分子、生理和行为水平，以了解时间协调在产生不同大脑状态中的作用和调节。 具体目标 1. 从睡眠到注意力的整个大脑的时间协调：大脑有多少参与？哪些地区？它们对于睡眠和注意力相同吗？ 2. 果蝇已知的唤醒系统对注意力和时间协调有什么影响？ 3. 时间协调的遗传扰动，不对称地和通过操纵连合，如何改变觉醒状态？ 公共卫生相关性：大脑时序紊乱是许多大脑疾病（包括自闭症和精神分裂症）的共同且潜在的关键特征。因此，更好地了解大脑不同部分之间的时序作用及其调节机制，将有助于我们解决与这些疾病相关的损伤的能力。