The Control of Active (REM) Sleep by the Amygdala
杏仁核对活跃 (REM) 睡眠的控制
基本信息
- 批准号:7354134
- 负责人:
- 金额:$ 40.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-12-15 至 2012-11-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAmygdaloid structureAnimalsAnxietyBehaviorBeliefBrain StemCataplexyCaviaCell NucleusCharacteristicsCholinergic AgentsCholinergic AgonistsCholinergic AntagonistsChronicClinicalConsensusDataDevelopmentDiseaseDisruptionEmotionalEmotionsFoundationsGenerationsGlutamatesHumanKnowledgeLinkMediatingMedicineMembraneMental DepressionMental disordersMicrodialysisMood DisordersMoodsMorphologyNarcolepsyNeurobiologyNeuronsNeurotransmittersPathologyPatternPhenotypePlayPontine structurePost-Traumatic Stress DisordersPreparationProceduresProcessPropertyProsencephalonREM SleepREM Sleep Behavior DisorderResearchRestless Legs SyndromeRoleSeriesSiteSleepSleep DisordersSourceStressSynapsesSystemTechniquesTestingTranslatingTranslational ResearchWakefulnessWorkbasecholinergicconceptdesigndisturbance in affectemotional factoremotional stimulusimprovedin vivoinsightinterdisciplinary approachmultidisciplinaryneuromechanismresearch studysleep regulationtransmission process
项目摘要
DESCRIPTION (provided by applicant): There is a consensus that active (REM) sleep occurs as a result of the discharge of executive active sleep-on neurons that are located in and/or within the vicinity of the nucleus pontis oralis (NPO); these neurons comprise the active sleep generator (AS-Generator). It is also universally accepted that the AS-Generator is activated by excitatory cholinergic projections from the laterodorsal and pedunculopontine nuclei (LDT/PPT). However, a variety of data suggest that other sites may also be capable of directly inducing active sleep by activating the AS-Generator. The direct electrophysiological and neurotransmitter bases for the control of active sleep-on neurons of the AS-Generator by these sites has not been examined, nor have interactions between the LDT/PPT and other sources of activation of the AS-Generator been explored. The research described in the proposal is designed to determine the veracity of the concept that, in addition to input from the LDT/PPT, neurons that are located in other sites, such as the central nucleus of the amygdala, are capable of directly activating the AS-Generator. Thus, we hypothesize that the central nucleus of he amygdala and the LDT/PPT not only function independently, but also work cooperatively, to control the onset, duration, termination and characteristics of the tonic and phasic periods of active sleep. Guided by the preceeding hypotheses and our Preliminary Studies, we intend to examine the control of the membrane properties, synaptic mechanisms and patterns of discharge of AS-Generator neurons in the NPO by neurons in the central nucleus of the amygdala. We will also examine the manner in which putative glutamatergic projections from neurons in the central nucleus of the amygdala interact with cholinergic projections from the LDT/PPT in initiating and maintaining active sleep. A multidisciplinary approach will be employed based upon the use of complementary techniques, procedures and neurobiological preparations in the chronic in vivo guinea pig preparation during spontaneously occurring states of sleep and wakefulness as well as during pharmalogically-induced active sleep. The data that are obtained and the verification of our hypotheses will provide important foundational bases for understanding the sites and neuronal mechanisms that control active sleep. We believe that these data will also be directly translatable to the development of rational therapies for the treatment of disorders of active sleep including REM Behavior Disorder, narcolepsy/cataplexy, and Restless Legs Syndrome. This knowledge will also provide a key foundation for a comprehensive approach to translational research to treat diverse pathologies that involve amygdala functions, especially those related to emotion and mood disorders, such as depression and PTSD, that also involve disruptions in the control of active sleep.
描述(由申请人提供):有一种共识认为,活跃(REM)睡眠是位于脑桥口核(NPO)内和/或附近的执行活跃睡眠神经元放电的结果;这些神经元组成了活跃睡眠生成器(AS-Generator)。人们还普遍认为,AS-Generator是由来自背外侧核和桥脑脚核的兴奋性胆碱能投射(LDT/PPT)激活的。然而,各种数据表明,其他网站可能也能够通过激活AS-Generator直接诱导活跃的睡眠。直接电生理和神经递质的基础,控制活跃的睡眠神经元的AS-生成器这些部位尚未被研究,也没有LDT/PPT与AS-生成器的其他激活来源之间的相互作用被探索。该提案中描述的研究旨在确定这一概念的准确性,即除了来自LDT/PPT的输入外,位于其他部位的神经元,如杏仁核中央核,也能够直接激活AS-Generator。因此,我们假设杏仁核中央核和LDT/PPT不仅独立运作,而且协同工作,控制活跃睡眠的强迫期和相期的开始、持续、终止和特征。在前面的假设和我们的初步研究的指导下,我们打算研究杏仁中央核神经元对NPO中AS-Generator神经元的膜特性、突触机制和放电模式的控制。我们还将研究杏仁中央核神经元的谷氨酸能投射与LDT/PPT的胆碱能投射在启动和维持活跃睡眠过程中相互作用的方式。将采用多学科的方法,在慢性活体豚鼠睡眠和清醒状态以及药物诱导的活跃睡眠中使用补充技术、程序和神经生物学制剂进行准备。所获得的数据和对我们假设的验证将为理解控制活跃睡眠的部位和神经机制提供重要的基础。我们相信,这些数据还将直接用于开发合理的治疗方法,用于治疗活动期睡眠障碍,包括快速眼动行为障碍、发作性睡病/痉挛和不宁腿综合征。这一知识还将为全面开展转化性研究提供关键基础,以治疗涉及杏仁核功能的各种病理,特别是与情绪和情绪障碍相关的疾病,如抑郁症和创伤后应激障碍,这些疾病也涉及活跃睡眠的控制中断。
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)
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MICHAEL H CHASE其他文献
MICHAEL H CHASE的其他文献
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{{ truncateString('MICHAEL H CHASE', 18)}}的其他基金
Resolution of the Mechanisms Responsible for Atonia during REM Sleep
解决快速眼动睡眠期间缺乏张力的机制
- 批准号:
8991865 - 财政年份:2015
- 资助金额:
$ 40.58万 - 项目类别:
Prevention of Hippocampal Neurodegeneration due to Age and Apnea
预防因年龄和呼吸暂停引起的海马神经变性
- 批准号:
8242626 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
Educational Program in Translational Sleep and Mental Health Research
转化睡眠和心理健康研究教育计划
- 批准号:
8530282 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
Educational Program in Translational Sleep and Mental Health Research
转化睡眠和心理健康研究教育计划
- 批准号:
8304908 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
Prevention of Hippocampal Neurodegeneration due to Age and Apnea
预防因年龄和呼吸暂停引起的海马神经变性
- 批准号:
8048193 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
Prevention of Hippocampal Neurodegeneration due to Age and Apnea
预防因年龄和呼吸暂停引起的海马神经变性
- 批准号:
8397579 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
Prevention of Hippocampal Neurodegeneration due to Age and Apnea
预防因年龄和呼吸暂停引起的海马神经变性
- 批准号:
8597383 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
Educational Program in Translational Sleep and Mental Health Research
转化睡眠和心理健康研究教育计划
- 批准号:
8179584 - 财政年份:2011
- 资助金额:
$ 40.58万 - 项目类别:
The Control of Active (REM) Sleep by the Amygdala
杏仁核对活跃 (REM) 睡眠的控制
- 批准号:
8197132 - 财政年份:2007
- 资助金额:
$ 40.58万 - 项目类别: