Fear learning alters primary sensory representations of threat-predictive stimuli
恐惧学习改变了威胁预测刺激的主要感官表征
基本信息
- 批准号:8686085
- 负责人:
- 金额:$ 38.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-01 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAfferent NeuronsAmericanAmygdaloid structureAnimalsAnxietyAnxiety DisordersAttentionBehaviorBehavioralBiological ModelsBrainBrain regionCalciumCell NucleusDataDevelopmentDiseaseDisease modelEmotionalEnvironmentExtinction (Psychology)FeedbackFrightImageLateralLeadLearningMeasuresMediatingMemoryMusNeuronal PlasticityOdorsOlfactory tractOpticsOutputPatientsPhasePlayPost-Traumatic Stress DisordersPresynaptic TerminalsProcessReactionResolutionRodentRodent ModelRoleSensorySensory ProcessShapesShockSignal TransductionStimulusStressSynapsesSystemTechniquesTestingTimeTrainingTraumabaseclassical conditioningconditioned fearconditioningeffective therapyexperiencein vivomemory retrievalmouse modelneurobiological mechanismneuroimagingneuromechanismneurotransmitter releaseolfactory bulboptical imagingpresynapticpreventpublic health relevancereceptorrelating to nervous systemresearch studyresponsesensory stimulussensory system
项目摘要
DESCRIPTION (provided by applicant): Fear learning permits an animal to respond adaptively to threatening circumstances (Bolles 1970). However, dysregulation of the brain's systems for fear learning can lead to debilitating anxiety disorders (Rosen and Schulkin 1998), including post-traumatic stress disorder (PTSD). In preliminary experiments in a mouse model of olfactory fear learning, longitudinal optical imaging experiments revealed large, associative, stimulus- specific increases in neurotransmitter release from olfactory sensory neurons (OSNs) when they are stimulated by fear-associated odors (CS+) in vivo. This neural response to the CS+ is enhanced after conditioning both compared to responses to neutral odors and compared to its own pre-conditioning baseline, thus showing that fear conditioning selectively changes the neural representation of the CS+ at the input to the brain. After fear conditioning, these primary sensory responses to footshock-predictive odors were actually larger than could be evoked by any concentration of that odor under control circumstances, perhaps serving as a "warning signal" to enhance reaction to the CS+ or to draw attention to it. This result suggests that changes in sensory processing of threat-related stimuli could play a role in anxiety disorders, which include a ubiquitous attentional bias toward dangerous or unpleasant stimuli. This project will combine optical neuroimaging, behavioral, and pharmacological techniques to investigate this learning-induced sensory neuroplasticity. The Specific Aims of the project are 1) to use various fear conditioning paradigms to determine the circumstances under which this sensory neuroplasticity occurs and how it relates to the formation of memories relating the odor and fear-inducing stimuli, 2) to learn the neural mechanisms by which this sensory neuroplasticity occurs, including the circuitry by which information about the fearful associations of CS+ reaches the primary sensory neurons, and 3) to discern how the change in the neural representation of the CS+ alters the brain's representation of sensory input both after normal emotional learning and in a rodent model of PTSD.
描述(由申请者提供):恐惧学习允许动物对威胁环境做出适应性反应(Bolles 1970)。然而,由于恐惧学习而导致的大脑系统调节失调可能会导致衰弱的焦虑症(Rosen和Schulkin 1998),包括创伤后应激障碍(PTSD)。在嗅觉恐惧学习的小鼠模型的初步实验中,纵向光学成像实验显示,当嗅觉感觉神经元(OSN)受到体内恐惧相关气味(CS+)刺激时,它们释放的神经递质大幅增加。无论是与中性气味的反应相比,还是与其自身的预适应基线相比,条件反射后对CS+的神经反应都得到了增强,从而表明恐惧条件作用选择性地改变了CS+在大脑输入端的神经表征。在恐惧条件作用后,这些对足部电击预测气味的初级感觉反应实际上大于在控制环境下任何浓度的这种气味所能唤起的,可能是增强对CS+的反应或引起人们注意的“警告信号”。这一结果表明,与威胁相关的刺激的感觉加工的变化可能在焦虑症中发挥作用,焦虑症包括普遍存在的对危险或令人不快的刺激的注意力偏向。这个项目将结合光学神经成像、行为和药理学技术来研究这种学习诱导的感觉神经可塑性。该项目的具体目标是1)使用各种恐惧条件反射范式来确定这种感觉神经可塑性发生的环境以及它与气味和恐惧诱导刺激相关的记忆形成的关系,2)了解这种感觉神经可塑性发生的神经机制,包括关于CS+恐惧联系的信息到达初级感觉神经元的回路,以及3)辨别CS+神经表征的变化如何改变大脑在正常情绪学习后和PTSD啮齿动物模型中对感觉输入的表征。
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 }}
John P McGann其他文献
John P McGann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('John P McGann', 18)}}的其他基金
How Fear Learning Alters Sensory Representations of Threat Predictive Stimuli
恐惧学习如何改变威胁预测刺激的感官表征
- 批准号:
10312005 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
How Fear Learning Alters Sensory Representations of Threat Predictive Stimuli
恐惧学习如何改变威胁预测刺激的感官表征
- 批准号:
10087959 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Cognitive modulation of primary sensory processing in olfactory receptor neurons
嗅觉受体神经元初级感觉处理的认知调节
- 批准号:
8595430 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Fear learning alters primary sensory representations of threat-predictive stimuli
恐惧学习改变了威胁预测刺激的主要感官表征
- 批准号:
8848430 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Fear learning alters primary sensory representations of threat-predictive stimuli
恐惧学习改变了威胁预测刺激的主要感官表征
- 批准号:
8561257 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Fear learning alters primary sensory representations of threat-predictive stimuli
恐惧学习改变了威胁预测刺激的主要感官表征
- 批准号:
9069084 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
How Fear Learning Alters Sensory Representations of Threat Predictive Stimuli
恐惧学习如何改变威胁预测刺激的感官表征
- 批准号:
10741571 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Sex differences in the neurophysiology of the olfactory system
嗅觉系统神经生理学的性别差异
- 批准号:
8803006 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Cognitive modulation of primary sensory processing in olfactory receptor neurons
嗅觉受体神经元初级感觉处理的认知调节
- 批准号:
8676775 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
Cognitive modulation of primary sensory processing in olfactory receptor neurons
嗅觉受体神经元初级感觉处理的认知调节
- 批准号:
9450926 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
相似海外基金
How Spinal Afferent Neurons Control Appetite and Thirst
脊髓传入神经元如何控制食欲和口渴
- 批准号:
DP220100070 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别:
Discovery Projects
The mechanisms of the signal transduction from brown adipocytes to afferent neurons and its significance.
棕色脂肪细胞向传入神经元的信号转导机制及其意义。
- 批准号:
23K05594 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10477437 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
- 批准号:
10315571 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10680037 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10654779 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10275133 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
- 批准号:
10470747 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
- 批准号:
RGPIN-2014-05517 - 财政年份:2018
- 资助金额:
$ 38.75万 - 项目类别:
Discovery Grants Program - Individual
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
- 批准号:
RGPIN-2014-05517 - 财政年份:2017
- 资助金额:
$ 38.75万 - 项目类别:
Discovery Grants Program - Individual