Function and Control of Hypothalamic Oscillators
下丘脑振荡器的功能和控制
基本信息
- 批准号:8770985
- 负责人:
- 金额:$ 19.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-08-22 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:AllelesArousalBehaviorBrainBrain regionCSNK1A1 geneCell NucleusCell physiologyCellsCharacteristicsChimera organismCircadian RhythmsContraceptive methodsCre-LoxPDevelopmentEstrogensFeedbackFertilityGene ExpressionGenerationsGenesGoalsHealthHumanHypothalamic structureInfertilityIngestionLeadLuteinizing HormoneMetabolic DiseasesMetabolismMethodsModelingModificationMusNeuronsNeurosecretory SystemsOrganOvulationPacemakersPatternPerformancePeripheralPhasePhysiologicalPhysiologyPreoptic AreasPublic HealthReproductionReproductive ProcessResearchRetinaRoleRunningSafetyScheduleSleepSystemTechnologyTestingTimecell typecircadian pacemakerdisorder riskimprovedkisspeptinmutantnoveloperationovulation timepublic health relevancereproductivereproductive successsuprachiasmatic nucleussystems researchtool
项目摘要
DESCRIPTION (provided by applicant): Fertility depends upon the appropriate timing of functions controlled by specialized neurons of the hypothalamus and preoptic area. The control of ovulation by the suprachiasmatic nucleus (SCN) is one of the best-established physiological functions of the circadian clock. The central question of this proposal is whether circadian oscillators in the SCN are not only necessary, but also sufficient, to explain the timing of the LH
surge. Circadian rhythms arise from the operation of well-defined transcriptional-translational feedback loops in which the oscillating expression of core clock genes is critical. These loops underlie circadian rhythms that take place not only in the SCN, but also in other brain regions and the periphery. Neither the extent nor the physiological importance of clock gene expression in specific cell types is well understood. Crosses between mice in which clock genes are floxed and lines bearing appropriate Cre drivers has led to exciting progress in studies of the peripheral organs and the retina, but application of this strategy to understanding the role of circadian rhythms in specific brain functions has not yet been accomplished. Circadian clocks appear to run not only in both GnRH cells which directly regulate the preovulatory LH surge and kisspeptinergic neurons from which they receive input. We will use Cre-Lox technology to determine not only the role of circadian function in each of these cell types, but also the importance for normal function of the coordination of phase and period of master and subordinate oscillators. First, we will selectively eliminate clock function by targeting Bmal1 in neurons that express GnRH or kisspeptin in order to determine whether the appropriate timing of the preovulatory LH surge depends upon local circadian oscillations. Second, we will selectively manipulate the period of master and subordinate oscillators to determine the consequences for the LH surge. Establishment of this approach will open new tools for understanding the mechanisms by which circadian systems coordinate behavior and physiology more generally. Given the pivotal role of neurons that contain such oscillators in a variety of homeostatic and reproductive processes, this research will reveal mechanisms that underlie metabolic diseases and infertility and lead to development of new therapies.
描述(申请人提供):生育能力取决于由下丘脑和视前区的专门神经元控制的功能的适当时机。视交叉上核(SCN)控制排卵是生物钟最成熟的生理功能之一。这一建议的中心问题是,是否SCN中的昼夜节律振荡器不仅是必要的,而且是足够的,来解释黄体生成素的时间
涌动。昼夜节律产生于定义明确的转录-翻译反馈环的操作,其中核心时钟基因的振荡表达是关键。这些环路构成了昼夜节律的基础,不仅发生在SCN,也发生在其他大脑区域和外周。时钟基因在特定细胞类型中表达的范围和生理意义都没有得到很好的理解。在带有时钟基因的小鼠和携带适当Cre驱动基因的品系之间的杂交,在外周器官和视网膜的研究中取得了令人兴奋的进展,但应用这一策略来理解昼夜节律在特定大脑功能中的作用尚未完成。生物钟似乎不仅在直接调节排卵前黄体生成素峰的GnRH细胞中运行,而且在它们接受输入的Kispeptin能神经元中运行。我们将使用CRE-Lox技术,不仅确定昼夜节律功能在每种细胞类型中的作用,而且确定主从振荡器的相位和周期协调对正常功能的重要性。首先,我们将选择性地通过靶向表达GnRH或Kispeptin的神经元上的BMal1来消除时钟功能,以确定排卵前促黄体生成素激增的适当时间是否取决于局部昼夜振荡。其次,我们将有选择地操纵主振荡器和从属振荡器的周期,以确定lh浪涌的后果。这一方法的建立将为更广泛地理解生理系统协调行为和生理的机制打开新的工具。鉴于包含这种振荡器的神经元在各种动态平衡和生殖过程中的关键作用,这项研究将揭示代谢性疾病和不孕不育的基础机制,并导致新疗法的开发。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ERIC L BITTMAN其他文献
ERIC L BITTMAN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ERIC L BITTMAN', 18)}}的其他基金
Generation of genetically engineered hamsters for circadian studies
用于昼夜节律研究的基因工程仓鼠的产生
- 批准号:
9343060 - 财政年份:2016
- 资助金额:
$ 19.34万 - 项目类别:
Generation of genetically engineered hamsters for circadian studies
用于昼夜节律研究的基因工程仓鼠的产生
- 批准号:
9224469 - 财政年份:2016
- 资助金额:
$ 19.34万 - 项目类别:
R21: Entrainment of Peripheral Circadian Rhythms
R21:周围昼夜节律的牵引
- 批准号:
7176583 - 财政年份:2007
- 资助金额:
$ 19.34万 - 项目类别:
R21: Entrainment of Peripheral Circadian Rhythms
R21:周围昼夜节律的牵引
- 批准号:
7352792 - 财政年份:2007
- 资助金额:
$ 19.34万 - 项目类别:
Suprachiasmatic Control of Peripheral Circadian Rhythms
周围昼夜节律的视交叉上控制
- 批准号:
7368075 - 财政年份:2005
- 资助金额:
$ 19.34万 - 项目类别:
Suprachiasmatic Control of Peripheral Circadian Rhythms
周围昼夜节律的视交叉上控制
- 批准号:
7033008 - 财政年份:2005
- 资助金额:
$ 19.34万 - 项目类别:
相似国自然基金
基于Valence-Arousal空间的维度型中文文本情感分析研究
- 批准号:61702443
- 批准年份:2017
- 资助金额:29.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Temporal dynamics of stress, sleep, and arousal in short-term risk for adolescentsuicidal behavior
青少年自杀行为短期风险中压力、睡眠和觉醒的时间动态
- 批准号:
10201876 - 财政年份:2019
- 资助金额:
$ 19.34万 - 项目类别:
Effects of alcohol intoxication and arousal on discounting and risk behavior
酒精中毒和兴奋对折扣和风险行为的影响
- 批准号:
8322920 - 财政年份:2011
- 资助金额:
$ 19.34万 - 项目类别:
Effects of alcohol intoxication and arousal on discounting and risk behavior
酒精中毒和兴奋对折扣和风险行为的影响
- 批准号:
8202346 - 财政年份:2011
- 资助金额:
$ 19.34万 - 项目类别:
The effects of attention, arousal, and reinforcement on welfare and behavior of intensively kept pigs
注意力、唤醒和强化对集约化饲养猪的福利和行为的影响
- 批准号:
5336165 - 财政年份:2001
- 资助金额:
$ 19.34万 - 项目类别:
Research Grants
SELF-REWARD, EMOTIONAL AROUSAL, AND PROSOCIAL BEHAVIOR
自我奖励、情绪唤醒和社交行为
- 批准号:
3052498 - 财政年份:1986
- 资助金额:
$ 19.34万 - 项目类别:
SELF-REWARD, EMOTIONAL AROUSAL, AND PROSOCIAL BEHAVIOR
自我奖励、情绪唤醒和社交行为
- 批准号:
3052497 - 财政年份:1985
- 资助金额:
$ 19.34万 - 项目类别:
ENDOCRINE DETERMINANTS OF SEXUAL BEHAVIOR AND AROUSAL
性行为和性唤起的内分泌决定因素
- 批准号:
3377060 - 财政年份:1984
- 资助金额:
$ 19.34万 - 项目类别:
ENDOCRINE DETERMINANTS OF SEXUAL BEHAVIOR AND AROUSAL
性行为和性唤起的内分泌决定因素
- 批准号:
3377061 - 财政年份:1984
- 资助金额:
$ 19.34万 - 项目类别:
Limbic System Activation During the Salt Arousal of Drinking Behavior in Animals
动物饮酒行为盐唤醒过程中边缘系统的激活
- 批准号:
68B3119 - 财政年份:1968
- 资助金额:
$ 19.34万 - 项目类别:
Limbic System Activation During the Salt Arousal of Drinking Behavior in Animals
动物饮酒行为盐唤醒过程中边缘系统的激活
- 批准号:
65B3119 - 财政年份:1965
- 资助金额:
$ 19.34万 - 项目类别: