Circadian control of structural plasticity in Drosophila

果蝇结构可塑性的昼夜节律控制

• 批准号: 8085756
• 负责人: Maria Fernanda Ceriani
• 金额: $ 5.23万
• 依托单位: FUNDACION INSTITUTO LELOIR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8085756
• 关键词: Activity Cycles; Acute; Adult; Affect; Animals; Award; Axon; Behavior; Behavior Control; Behavioral; Biochemical; Biological Clocks; Biological Models; Biological Phenomena; Brain; CREB1 gene; Calcium; Caliber; Cell Culture Techniques; Cells; Chemicals; Circadian Rhythms; Clock protein; Complement; Coupled; Cyclic AMP; Dendrites; Development; Dorsal; Drosophila genus; Electron Microscopy; Employee Strikes; Environment; Fruit; Gene Expression; Genetic; Genetic Techniques; Genetic Transcription; Goals; Grant; Image; Immunofluorescence Immunologic; Immunohistochemistry; Interneurons; Label; Light; Link; Mammals; Membrane; Metabolism; Molecular; Monitor; Morphology; Motor Activity; Muscle fasciculation; Neuraxis; Neuromuscular Junction; Neurons; Organism; Output; Pacemakers; Pathway interactions; Periodicity; Peripheral; Physiological; Physiology; Pigments; Play; Preparation; Presynaptic Terminals; Property; Reporter; Reporting; Rest; Role; Rotation; Screening procedure; Signal Pathway; Sleep; Structure; Study models; Sum; Synapses; System; Therapeutic; Thinking; Time; Tissues; Transgenic Organisms; Transmission Electron Microscopy; Voltage-Gated Potassium Channel; base; circadian pacemaker; environmental change; extracellular; fly; in vivo; nodal myocyte; novel; parent grant; presynaptic; programs; public health relevance; sleep regulation; suprachiasmatic nucleus; synaptogenesis; tissue fixing; tool; transmission process

DESCRIPTION (provided by applicant): The circadian clock serves as a temporal filter to time gene expression, cell metabolism, physiology and behavior to the most critical moments in the day, thus contributing to the organism's adaptation to a changing environment. While the molecular mechanisms that generate and sustain rhythmicity at the cellular level are well understood, it is less clear how this information is further structured to control specific behavioral outputs. Rhythmic release of pigment dispersing factor (PDF) has been proposed to propagate the (time of day) information from core pacemaker (PDF reactive) cells to downstream targets underlying rhythmic locomotor activity. Indeed, such circadian changes in PDF intensity represent the only known mechanism through which the PDF circuit could communicate with its output. Recently, we reported a novel circadian phenomenon involving extensive remodeling in the axonal terminals of the PDF circuit which display higher complexity during the day and significantly lower complexity at nighttime. Thus, clock-controlled structural plasticity could be a candidate mechanism contributing to the transmission of the information downstream of pacemaker cells. The aim of the present proposal is to extend this initial observation and characterize the structure of the PDF circuit by time- lapse imaging in cultured brains. This approach, coupled with immunohistochemistry, will shed light on whether synaptogenesis and synapse elimination is concomitantly taking place. In addition, the molecular mechanisms responsible for such substantial remodeling will be explored employing novel genetic tools that allow spatial and temporal control of gene expression. Gaining understanding in a model system like Drosophila most likely will impact the current thinking of how the clock controls sleep/activity cycles in mammals. PUBLIC HEALTH RELEVANCE: Circadian systems evolved as a mechanism that allows organisms to adapt to the environmental changes in light and dark which occur as a consequence of the rotation of the Earth. Because of its unique repertoire of genetic tools, Drosophila is a well established model for the study of the circadian clock. Although the biochemical components underlying the molecular oscillations have been characterized in detail, the mechanisms used by clock neurons to convey information to the downstream pathways remain elusive. We have recently discovered a novel form of network plasticity whereby a circuit that is central to rhythmic rest-activity cycles undergoes substantial circadian remodeling and might be critical for clock control of behavior. The aim of this proposal is to extend the initial observations and characterize the molecular mechanisms underlying this form of structural plasticity. Thus, this project will shed light into some novel mechanisms by which neuronal circadian clocks regulate physiology and behavior.

描述（由申请人提供）：生物钟充当时间过滤器，将基因表达、细胞代谢、生理和行为计时到一天中最关键的时刻，从而有助于生物体适应不断变化的环境。虽然在细胞水平上产生和维持节律性的分子机制已被很好地理解，但尚不清楚如何进一步构建这些信息以控制特定的行为输出。色素分散因子 (PDF) 的节律性释放已被提议将（一天中的时间）信息从核心起搏器（PDF 反应性）细胞传播到节律性运动活动的下游目标。事实上，PDF 强度的这种昼夜节律变化代表了 PDF 电路与其输出进行通信的唯一已知机制。最近，我们报道了一种新颖的昼夜节律现象，涉及 PDF 电路轴突末端的广泛重塑，其在白天表现出更高的复杂性，而在夜间表现出显着较低的复杂性。因此，时钟控制的结构可塑性可能是有助于起搏细胞下游信息传输的候选机制。本提案的目的是扩展这一初步观察，并通过培养大脑中的延时成像来表征 PDF 电路的结构。这种方法与免疫组织化学相结合，将揭示突触发生和突触消除是否同时发生。此外，将利用允许基因表达的空间和时间控制的新型遗传工具来探索负责这种实质性重塑的分子机制。了解像果蝇这样的模型系统很可能会影响当前对生物钟如何控制哺乳动物睡眠/活动周期的思考。 公共健康相关性：昼夜节律系统是作为一种机制进化而来的，它使生物体能够适应因地球自转而发生的明暗环境变化。由于其独特的遗传工具库，果蝇是研究生物钟的成熟模型。尽管分子振荡背后的生化成分已被详细表征，但时钟神经元用于将信息传递到下游途径的机制仍然难以捉摸。我们最近发现了一种新形式的网络可塑性，其中作为有节奏的休息-活动周期的核心的电路经历了实质性的昼夜节律重塑，并且可能对于行为的时钟控制至关重要。该提案的目的是扩展最初的观察并表征这种结构可塑性形式背后的分子机制。因此，该项目将揭示神经元生物钟调节生理和行为的一些新机制。