Fear Entrainment of Circadian Rhythms
昼夜节律的恐惧夹带
基本信息
- 批准号:10539261
- 负责人:
- 金额:$ 33.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-12-01 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:ARNTL geneAmygdaloid structureAnimalsAnxietyAnxiety DisordersAreaArrhythmiaBehaviorBehavioralBiological ClocksBiological RhythmBioluminescenceBrainCircadian RhythmsComplexCuesDangerousnessDarknessDiseaseElectric StimulationElementsEnterobacteria phage P1 Cre recombinaseEstrous CycleExposure toFeeding behaviorsFemaleFoodFrightGene ExpressionGene TargetingGenesGenetic TranscriptionGoalsHalorhodopsinsIn VitroInjectionsKnock-outLaboratoriesLightLinkLocationMammalsMolecularMusNeuronsOpticsOrganOutputOvarian hormonePerceptionPeriodicityPeripheralPhasePost-Traumatic Stress DisordersProcessProsencephalonProtocols documentationRattusRodentRunningSex DifferencesShockSleep DisordersSleep Wake CycleSliceStimulusSystemTestingTimeTraumaViralWaterWorkcircadiancircadian pacemakerconditioned fearexperimental studyfeedingfoothormone regulationin vivomalemolecular clockneuromechanismoptogeneticsresponsesleep regulationsuprachiasmatic nucleustranscription factor
项目摘要
SUMMARY
Recent work in our laboratory has shown that cyclic fear can prevail over entrainment of circadian rhythms by
the light-dark (LD) cycle and lead to diurnal foraging and feeding in nocturnal rodents. When mice or rats are
housed in a cage setup in which they need to leave a safe nesting area to access a foraging area for food and
water, they forage and feed during the dark phase of the LD cycle. If the foraging area is rendered dangerous
with random footshocks during the active dark phase, the animals’ foraging and feeding activity shifts to the
light phase. This switch to diurnal behavior represents the output of a circadian oscillator, which is entrained by
the cyclic fear stimulus, and is dependent on an intact suprachiasmatic nucleus (SCN), where the master clock
resides, and an intact amygdala, which encodes fear perception. Our working hypothesis for this proposal is
that a circadian oscillator within the amygdala is entrained by cyclic fear and leads to a shift in the timing of
foraging and feeding behavior.
Specific Aim 1 will determine whether cyclic nocturnal fear entrains the circadian oscillators in the amygdala
and/or the SCN in animals entrained to cyclic fear under LD or constant darkness (DD) conditions.
Specific Aim 2 will determine whether cyclic fear can also entrain the circadian rhythms of foraging and feeding
in female mice, and whether sex differences are explained by the ovarian hormone regulation.
Specific Aim 3 will determine whether the evocation of fear by electrical or optogenetic stimulation of the
basolateral amygdala (BLA) during the dark phase is sufficient to induce entrainment of feeding and foraging,
and whether the activation of the BLA is necessary for fear entrainment by optogenetically inhibiting it while
animals are exposed to the fear stimulus. This Aim will also assess whether in vitro optogenetic stimulation of
the amygdala is sufficient to locally entrain the amygdala circadian oscillator.
Specific Aim 4A,B will exploit region-specific KOs of the clock gene Bmal1 or global KOs of the clock genes
Per1 and Per2 to determine whether canonical molecular clock of mammals is part of the fear-entrained
oscillator. Aim 4C will assess whether amygdala-specific Bmal1 KOS fail to entrain to cyclic fear.
Our finding that nocturnal fear entrains circadian rhythms indicates that limbic centers that encode fear are part
of the circuitry that orchestrates circadian rhythms. It also provides a uniquely tractable system to unmask how
the master circadian clock within the SCN and the amygdala integrate photic and fear cues to time complex
behavioral processes. Circadian and sleep disorders are a hallmark of anxiety and fear disorders such as post-
traumatic stress disorder; our findings could shed light into the neural mechanisms that link trauma to the
regulation of sleep and circadian rhythms.
概括
我们实验室最近的工作表明,周期性恐惧可以通过以下方式战胜昼夜节律的影响:
光-暗(LD)循环并导致夜间啮齿动物昼间觅食和进食。当小鼠或大鼠
它们被安置在笼子里,需要离开安全的筑巢区才能进入觅食区寻找食物和
水,它们在 LD 周期的黑暗阶段觅食和进食。如果觅食区域变得危险
在活跃的黑暗阶段,通过随机的足部震动,动物的觅食和进食活动转移到
光相。这种向昼夜行为的转变代表了昼夜节律振荡器的输出,它受到
周期性恐惧刺激,并且依赖于完整的视交叉上核(SCN),其中主时钟
存在着一个完整的杏仁核,它编码恐惧知觉。我们对该提案的工作假设是
杏仁核内的昼夜节律振荡器受到周期性恐惧的影响,并导致时间发生变化
觅食和摄食行为。
具体目标 1 将确定周期性夜间恐惧是否会影响杏仁核中的昼夜节律振荡器
和/或在 LD 或持续黑暗 (DD) 条件下陷入周期性恐惧的动物的 SCN。
具体目标 2 将确定周期性恐惧是否也能影响觅食和进食的昼夜节律
在雌性小鼠中,以及性别差异是否可以通过卵巢激素调节来解释。
具体目标 3 将确定是否通过电刺激或光遗传学刺激引起恐惧
基底外侧杏仁核(BLA)在黑暗阶段足以诱导摄食和觅食,
以及 BLA 的激活是否对于通过光遗传学抑制它来夹带恐惧是必要的
动物受到恐惧刺激。该目标还将评估体外光遗传学刺激是否
杏仁核足以局部带动杏仁核昼夜节律振荡器。
具体目标 4A,B 将利用时钟基因 Bmal1 的区域特异性 KO 或时钟基因的全局 KO
Per1和Per2确定哺乳动物的规范分子钟是否是恐惧的一部分
振荡器。目标 4C 将评估杏仁核特异性 Bmal1 KOS 是否无法引发周期性恐惧。
我们发现夜间恐惧会影响昼夜节律,这表明编码恐惧的边缘中枢是其中的一部分
协调昼夜节律的电路。它还提供了一个独特的易于处理的系统来揭示如何
SCN 和杏仁核内的主生物钟将光和恐惧线索整合到时间复合体中
行为过程。昼夜节律和睡眠障碍是焦虑和恐惧症的标志,例如后遗症。
创伤性应激障碍;我们的发现可以揭示将创伤与创伤联系起来的神经机制
睡眠和昼夜节律的调节。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Sleep and the circadian system: The latest gossip on a tumultuous long-term relationship.
- DOI:10.1016/j.nbscr.2021.100061
- 发表时间:2021-05
- 期刊:
- 影响因子:0
- 作者:Sanchez REA;de la Iglesia HO
- 通讯作者:de la Iglesia HO
Sleep timing and the circadian clock in mammals: Past, present and the road ahead.
睡眠时间和哺乳动物的昼夜节律:过去,现在和前进的道路。
- DOI:10.1016/j.semcdb.2021.05.034
- 发表时间:2022-06
- 期刊:
- 影响因子:7.3
- 作者:Sanchez REA;Kalume F;de la Iglesia HO
- 通讯作者:de la Iglesia HO
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Horacio O De La Iglesia其他文献
Horacio O De La Iglesia的其他文献
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{{ truncateString('Horacio O De La Iglesia', 18)}}的其他基金
Regulation of Circadian Rhythms and Sleep by The Lunar Month
农历月份对昼夜节律和睡眠的调节
- 批准号:
10514347 - 财政年份:2022
- 资助金额:
$ 33.1万 - 项目类别:
Circadian Structural Plasticity in Central Pacemakers
中央起搏器的昼夜节律结构可塑性
- 批准号:
10287332 - 财政年份:2021
- 资助金额:
$ 33.1万 - 项目类别:
The Society for Research on Biological Rhythms Conference: The Implications of Biological Rhythms for Health and Society
生物节律研究学会会议:生物节律对健康和社会的影响
- 批准号:
9543207 - 财政年份:2018
- 资助金额:
$ 33.1万 - 项目类别:
Role of GABA on circadian and homeostatic regulation of sleep
GABA 对昼夜节律和睡眠稳态调节的作用
- 批准号:
9128731 - 财政年份:2015
- 资助金额:
$ 33.1万 - 项目类别:
Role of GABA on circadian and homeostatic regulation of sleep
GABA 对昼夜节律和睡眠稳态调节的作用
- 批准号:
9004847 - 财政年份:2015
- 资助金额:
$ 33.1万 - 项目类别:
Communication in the Mammalian Circadian Clock: The Role of Nitric Oxide
哺乳动物昼夜节律钟中的通讯:一氧化氮的作用
- 批准号:
8011525 - 财政年份:2009
- 资助金额:
$ 33.1万 - 项目类别: