Influence of the locus coeruleus on fear learning and threat processing in the ventral hippocampus
Influence of the locus coeruleus on fear learning and threat processing in the ventral hippocampus
批准号:
10552594
负责人:
Brian J Wiltgen
金额:
$19.41万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-01-20 至 2023-12-31
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
中文摘要
摘要
蓝斑(LC)和腹侧海马区(VHPC)都影响我们对威胁刺激的反应。
到目前为止,研究主要集中在这些结构中的每一种对恐惧学习和
焦虑。然而,很少有研究研究LC和vHPC之间的相互作用
威胁处理。LC通常被认为向HPC和其他大脑区域提供显著信号,
这增强了可塑性,促进了记忆的形成。但是,LC和vHPC也已显示
在有压力的情况下推动与生俱来的焦虑相关行为。为了解决这一明显的差异,我们将
测试恐惧学习和天生焦虑都是由LC中不同的振荡控制的新想法
在遇到威胁时传输到vHPC。尖锐的,令人恐惧的
刺激已被证明在LC和vHPC中产生大的瞬时反应。例如,厌恶
足底电击在两个结构中产生相性活动,在运动后可持续几秒钟
刺激计划已经终止。由于阶段性LC反应通常与注意力集中有关,而
编码显著刺激,我们假设LC中的阶段活动通过增强
VHPC中的冲击处理。相比之下,导致焦虑的情况,如开放的,没有庇护
在环境中,LC中的补药活性会产生较小但更持久的增加。因此,我们
假设LC在遇到潜在威胁时会引发焦虑相关行为
在vhpc中发射主音。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
利用细胞型特定光遗传学在操作LC的同时监测vHPC活性的光度学
在恐惧条件反射和引发焦虑的情况下的神经元。后续研究将建立在这些基础上
结果采用体内钙显像法测定强直性和相性LC放电对心肌细胞活性的影响。
VHPC中的休克反应细胞和焦虑反应细胞。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
The role of novelty and surprise in aversive conditioning
-
批准号:10682277
-
项目类别:
-
资助金额:$58.15万
-
财政年份:2023
-
负责人:Brian J Wiltgen
-
依托单位:
The contribution of the hippocampus to learned opiate tolerance
-
批准号:10586097
-
项目类别:
-
资助金额:$19.43万
-
财政年份:2022
-
负责人:Brian J Wiltgen
-
依托单位:
The role of novelty and surprise in aversive conditioning
-
批准号:10626682
-
项目类别:
-
资助金额:$55.48万
-
财政年份:2022
-
负责人:Brian J Wiltgen
-
依托单位:
The contribution of the hippocampus to learned opiate tolerance
-
批准号:10392284
-
项目类别:
-
资助金额:$23.29万
-
财政年份:2022
-
负责人:Brian J Wiltgen
-
依托单位:
Influence of the locus coeruleus on fear learning and threat processing in the ventral hippocampus
-
批准号:10391884
-
项目类别:
-
资助金额:$23.2万
-
财政年份:2022
-
负责人:Brian J Wiltgen
-
依托单位:
Tools for Dissecting Proximal and Distal CA1 Contributions to Learning and Memory
-
批准号:9455391
-
项目类别:
-
资助金额:$18.52万
-
财政年份:2017
-
负责人:Brian J Wiltgen
-
依托单位:
Neurobiological Mechanisms of Systems Consolidation
-
批准号:9070016
-
项目类别:
-
资助金额:$33.35万
-
财政年份:2015
-
负责人:Brian J Wiltgen
-
依托单位:
Motivational control of goal-directed actions and habits
-
批准号:7876013
-
项目类别:
-
资助金额:$7.7万
-
财政年份:2010
-
负责人:Brian J Wiltgen
-
依托单位:
Memory following CaMKII Loss in Hippocampal Subregions
-
批准号:7007255
-
项目类别:
-
资助金额:$4.88万
-
财政年份:2004
-
负责人:Brian J Wiltgen
-
依托单位:
Memory following CaMKII Loss in Hippocampal Subregions
-
批准号:6738530
-
项目类别:
-
资助金额:$3.97万
-
财政年份:2004
-
负责人:Brian J Wiltgen
-
依托单位:
Memory following CaMKII Loss in Hippocampal Subregions
-
批准号:6815813
-
项目类别:
-
资助金额:$4.4万
-
财政年份:2004
-
负责人:Brian J Wiltgen
-
依托单位:
海外基金