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Investigating circadian communication within the brain and body

研究大脑和身体内的昼夜节律交流

基本信息

批准号：
8278631
负责人：
Jennifer Anne Evans
金额：
$ 5.77万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
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：
2010-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8278631
关键词：
Address Affective Area Behavior Behavioral Biological Models Bioluminescence Brain Brain region Cardiovascular Diseases Cells Circadian Rhythms Communication Complex Coupling Cues Darkness Data Development Dissociation Dorsal Exposure to Firefly Luciferases Functional disorder Gene Expression Goals Health Histocompatibility Testing Human Human Biology Image Image Analysis Immunohistochemistry In Vitro Individual Laboratories Lead Length Light Lighting Link Malignant Neoplasms Mammals Mediating Metabolic Metabolic Diseases Modeling Molecular Monitor Mood Disorders Mus Neurons Neurophysiology - biologic function Neurosciences Output Pacemakers Pathology Pathway interactions Pharmacology Phase Photoperiod Physiological Physiology Production Regulation Reporter Research Rest Rodent Seasons Signal Transduction Sleep Slice System Testing Time Tissues Training Transgenic Mice base circadian pacemaker cognitive function day length environmental change experience immune function in vivo insight mouse model novel diagnostics novel therapeutic intervention relating to nervous system reproductive function shift work skills suprachiasmatic nucleus

项目摘要

How oscillators within the SCN interact with one another and the rest of the brain remains an ill-defined but critical area of research. Different regions of the SCN project to largely overlapping brain regions; however, it is unknown whether output pathways from each region convey redundant or distinct signals. To assess regional interactions and the functional contribution of different SCN regions, I have dissociated rhythms in the dorsal and ventral SCN using an in vivo photoperiodic manipulation. To track the phase of individual neurons within the SCN, we employ real-time bioluminescence imaging of SCN slices from the PER2:LUC mouse, a transgenic mouse model where a PER2 production within individual cells is monitored using a firefly luciferase reporter. In preliminary studies, I have used an ultra long photoperiod (20h light: 4h darkness, LD 20:4) to reorganize the SCN into dorsal and ventral regions that express dissociated rhythms on the first cycle in vitro. Over the subsequent cycles in vitro, the phase difference between dorsal and ventral SCN is reduced, suggesting that dissociated regions interact in vitro. I propose to test the hypotheses 1) that changes in phase relationships over time in vitro depend on coupling between SCN regions and 2) that dorsal and ventral SCN convey functionally distinct timing signals to downstream tissues. To investigate these questions, I will use real-time bioluminescence imaging of multiple tissue types, advanced computational analyses of the imaging data, pharmacological manipulations, and immunohistochemistry for clock gene expression in SCN targets. My long-term objective is to understand how neural oscillators within the SCN interact to form a functional pacemaker capable of regulating rhythms in behavior and physiology.

SCN内的振荡器如何相互作用以及大脑的其他部分仍然是一个定义不清但关键的研究领域。SCN的不同区域投射到很大程度上重叠的大脑区域;然而，尚不清楚每个区域的输出通路是否传递冗余或不同的信号。为了评估区域的相互作用和不同的SCN区域的功能贡献，我解离的节奏在背侧和腹侧SCN使用在体内的光周期操作。为了跟踪SCN内单个神经元的相位，我们采用来自PER 2：LUC小鼠的SCN切片的实时生物发光成像，所述PER 2：LUC小鼠是一种转基因小鼠模型，其中使用萤火虫荧光素酶报告基因监测单个细胞内的PER 2产生。在初步研究中，我已经使用了超长的光周期（20小时光：4小时黑暗，LD 20：4）重组SCN背侧和腹侧区域，表达解离的节奏在体外的第一个周期。在随后的体外循环中，背侧和腹侧SCN之间的相位差减小，表明解离区域在体外相互作用。我建议测试的假设1）在体外的相位关系随时间的变化取决于SCN区域之间的耦合和2）背侧和腹侧SCN传达功能不同的定时信号到下游组织。为了研究这些问题，我将使用多种组织类型的实时生物发光成像，成像数据的高级计算分析，药理学操作和SCN靶点中时钟基因表达的免疫组织化学。我的长期目标是了解SCN内的神经振荡器如何相互作用，形成一个能够调节行为和生理节律的功能性起搏器。