Influence of the locus coeruleus on fear learning and threat processing in the ventral hippocampus
蓝斑对腹侧海马恐惧学习和威胁处理的影响
基本信息
- 批准号:10552594
- 负责人:
- 金额:$ 19.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-20 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAmericanAmygdaloid structureAnxietyAnxiety DisordersAttentionAttention deficit hyperactivity disorderBehaviorBehavioralBipolar DisorderBrain regionCatecholaminesCellsCognitiveDiseaseEnvironmentFiberFollow-Up StudiesFrightGoalsHippocampusHormonesHumanHypothalamic structureImageLateralLearningLesionMediatingMemoryMemory impairmentMental disordersMonitorNeuronsOutputPathway interactionsPhasePhotometryPhysiologicalPlayProcessProductionResearchRoleSchizophreniaShockSignal TransductionStimulusStressStructureSystemTestingTrainingUnited StatesUnited States National Institutes of Healthanxiety reductionanxiety-related behaviorcell typecomorbidityconditioned fearexperienceexperimental studyfollow-upin vivoin vivo calcium imaginginterdisciplinary approachlocus ceruleus structureneuralneuromechanismneuroregulationnoveloptogeneticspreventresponsetransmission process
项目摘要
Abstract
The locus coeruleus (LC) and ventral hippocampus (vHPC) both influence our response to threatening stimuli.
Research to date has focused primarily on the contribution each of these structures makes to fear learning and
anxiety. However, few studies have examined the interactions that occur between the LC and vHPC during
threat processing. The LC is typically thought to provide a salience signal to the HPC and other brain regions,
that enhances plasticity and facilitates memory formation. However, the LC and vHPC have also been shown
to drive innate anxiety-related behaviors in stressful situations. To resolve this apparent discrepancy, we will
test the novel idea that fear learning and innate anxiety are both controlled by distinct oscillations in the LC
(phasic vs tonic firing) that are transmitted to the vHPC when a threat is encountered. Acute, fear-inducing
stimuli have been shown to produce large, transient responses in the LC and the vHPC. For example, aversive
footshock produces phasic activity in both structures that can persist for up to several seconds after the
stimulus has terminated. As phasic LC responses are typically associated with focused attention and the
encoding of salient stimuli, we hypothesize that phasic activity in the LC promotes fear learning by enhancing
shock processing in the vHPC. In contrast, situations that induce anxiety, such as open, unsheltered
environments, produce smaller, but longer lasting increases in tonic activity in the LC. Consequently, we
hypothesize that the LC elicits anxiety-related behaviors when a potential threat is encountered by inducing
tonic firing in the vHPC. To test these ideas, we will use a multidisciplinary approach that combines in vivo fiber
photometry with cell-type specific optogenetics to simultaneously monitor vHPC activity while manipulating LC
neurons during fear conditioning and situations that provoke anxiety. Follow-up studies will build on these
results by using in vivo calcium imaging to determine the effects of tonic and phasic LC firing on the activity of
shock-responsive and anxiety-responsive cells in the vHPC.
抽象的
院位(LC)和腹侧海马(VHPC)都会影响我们对威胁刺激的反应。
迄今为止的研究主要集中在这些结构中的每一个对恐惧学习和
焦虑。但是,很少有研究检查LC和VHPC之间发生的相互作用
威胁处理。通常认为LC为HPC和其他大脑区域提供显着信号,
这可以增强可塑性并促进记忆形成。但是,LC和VHPC也已显示
在压力很大的情况下推动与先天焦虑相关的行为。为了解决这一明显的差异,我们将
测试新的想法,即恐惧学习和天生的焦虑都由LC中的独特振荡控制
遇到威胁时,(Phasic vs Tonic射击)将传输到VHPC。敏锐,恐惧引起
刺激已显示出在LC和VHPC中产生较大的短暂反应。例如,厌恶
脚印在两种结构中都产生阶段活性,在
刺激已终止。由于阶段LC的反应通常与集中注意力相关联,并且
我们假设LC中的阶段活动可以通过增强来促进恐惧学习
VHPC中的冲击处理。相比之下,引起焦虑的情况,例如开放,毫无用处
环境,在LC中产生较小但持久的增长持续增加。因此,我们
假设LC通过诱导遇到潜在威胁时会引起与焦虑相关的行为
在VHPC中发射补品。为了测试这些想法,我们将使用一种结合体内纤维的多学科方法
用细胞型特异性光遗传学的光度法同时监测VHPC活性,同时操纵LC
在恐惧调节和促使焦虑的情况下的神经元。后续研究将基于这些
通过使用体内钙成像来确定滋补和阶段LC触发对活性的影响
VHPC中的休克反应和焦虑响应性细胞。
项目成果
期刊论文数量(0)
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Brian J Wiltgen其他文献
Brian J Wiltgen的其他文献
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{{ truncateString('Brian J Wiltgen', 18)}}的其他基金
The role of novelty and surprise in aversive conditioning
新奇和惊喜在厌恶性条件反射中的作用
- 批准号:
10682277 - 财政年份:2023
- 资助金额:
$ 19.41万 - 项目类别:
The contribution of the hippocampus to learned opiate tolerance
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10586097 - 财政年份:2022
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$ 19.41万 - 项目类别:
The contribution of the hippocampus to learned opiate tolerance
海马体对习得阿片耐受性的贡献
- 批准号:
10392284 - 财政年份:2022
- 资助金额:
$ 19.41万 - 项目类别:
Influence of the locus coeruleus on fear learning and threat processing in the ventral hippocampus
蓝斑对腹侧海马恐惧学习和威胁处理的影响
- 批准号:
10391884 - 财政年份:2022
- 资助金额:
$ 19.41万 - 项目类别:
The role of novelty and surprise in aversive conditioning
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- 批准号:
10626682 - 财政年份:2022
- 资助金额:
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Tools for Dissecting Proximal and Distal CA1 Contributions to Learning and Memory
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Neurobiological Mechanisms of Systems Consolidation
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Memory following CaMKII Loss in Hippocampal Subregions
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Memory following CaMKII Loss in Hippocampal Subregions
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