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：
9069084
负责人：
John P McGann
金额：
$ 38.75万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
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 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9069084
关键词：
Adult Afferent Neurons American Amygdaloid structure Animals Anxiety Anxiety Disorders Attention Behavior Behavioral Biological Models Brain Brain region Calcium Cell Nucleus Data Development Disease Disease model Emotional Environment Extinction (Psychology)Feedback Fright Image Lateral Lead Learning Measures Mediating Memory Mus Neuronal Plasticity Odors Olfactory tract Optics Output Patients Phase Play Post-Traumatic Stress Disorders Presynaptic Terminals Process Reaction Rodent Rodent Model Role Sensory Sensory Process Shapes Shock Signal Transduction Stimulus Stress Synapses System Techniques Testing Time Training Trauma attentional bias base behavioral response classical conditioning conditioned fear conditioning effective therapy experience in vivo memory retrieval mouse model neurobiological mechanism neuroimaging neuromechanism neurotransmitter release olfactory bulb olfactory sensory neurons optical imaging presynaptic prevent public health relevance receptor relating to nervous system research study response sensory input sensory stimulus sensory system temporal measurement

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（由申请人提供）：恐惧学习允许动物适应威胁情况（Bolles 1970）。然而，恐惧学习的大脑系统失调会导致使人衰弱的焦虑症（Rosen and Schulkin 1998），包括创伤后应激障碍（PTSD）。在嗅觉恐惧学习的小鼠模型中的初步实验中，纵向光学成像实验表明，当嗅觉感觉神经元（OSN）在Vivo In vivo中刺激了嗅觉感觉神经元（OSN），从嗅觉感觉神经元（OSN）中释放神经递质的大量，刺激性刺激特异性增加。与对中性气味的反应相比，与其自身的预处理基线相比，对CS+的这种神经反应得到了增强，因此表明恐惧条件选择性地改变了大脑输入处CS+的神经表示。在恐惧条件下，这些对脚部预测性气味的主要感觉反应实际上比在控制情况下的任何浓度所吸引的任何浓度所吸引的脚感更大，也许是“警告信号”，以增强对CS+的反应或引起人们对它的注意。该结果表明，与威胁相关刺激的感觉处理的变化可能在焦虑症中发挥作用，其中包括无处不在的注意力偏见危险或不愉快的刺激。该项目将结合光学神经影像，行为和药理技术，以研究这种学习引起的感觉神经塑性。项目的具体目的是1）使用各种恐惧条件范式来确定这种感觉神经塑性发生的情况，以及与气味和恐惧诱导刺激相关的记忆形成的关系，2）学习神经机制，通过该神经机制，包括恐惧的感觉，包括恐惧的感觉，包括恐惧的信息，这些信息+与该信息相关的信息，这些信息是相关的。 3）辨别CS+神经表示的变化如何在正常的情绪学习和PTSD模型中改变大脑对感觉输入的表示。