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Stress modulation of olfactory sensation

嗅觉的压力调节

基本信息

批准号：
10055972
负责人：
LISA STOWERS
金额：
$ 63.5万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2021-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10055972
关键词：
Ablation Adrenal Glands Adrenal hormone preparation Adult Afferent Neurons American Anxiety Behavior Behavioral Brain Calcium Cues Data Detection Diestrus Drug Targeting Environment Epithelial Esthesia Female Gender Gene Expression Profile Genetic Goals Hormonal Hormone Receptor Hormones Human Image Immunohistochemistry Impairment Individual Knowledge Mammals Measures Mediating Modeling Molecular Mus National Institute of Mental Health Nature Neurons Neurophysiology - biologic function Odors Olfactory Epithelium Olfactory Pathways Periodicity Pharmaceutical Preparations Pharmacology Pheromone Probability Production Public Health Publishing Reporting Research Sensory Signal Transduction Smell Perception Stress Therapeutic Vacuum Work acute stress base behavior change biological adaptation to stress experimental study in vivo imaging inhibitor/antagonist male neural correlate neuromechanism olfactory sensory neurons olfactory stimulus prevent receptor receptor expression relating to nervous system response restraint restraint stress sensory mechanism sensory system stress state

项目摘要

The aims of this proposal will determine mechanisms by which the internal state of stress alters neural activity. Even the most logical and brilliant can suddenly turn incoherent when riddled with anxiety. Strikingly, twenty percent of adult Americans suffer from debilitating stress. The inability to faithfully find stress-responsive neurons throughout the brain has stalled the field's ability to discover the mechanisms of precisely how stress impacts neurons to alter behavior. What is needed is a robust experimental platform for us and others to reliably use as a model to investigate how the internal state of stress alters neural function and behavior. Our preliminary data indicates that the state of stress silences subsets of neural activity in easily identified, well defined subsets of mouse olfactory sensory neurons. Stress silencing of neural activity has a black and white effect on behavior; if an individual cannot sense an odor cue they do not appropriately respond to the environment. In itself, this is surprising because it has been thought that the olfactory system is just a passive sensory collector vacuuming up environmental cues and passing that information to the brain. Instead, our preliminary data reveals that olfactory sensory neurons are capable of responding to an individual's current stress state, and that this response inhibits the sensation of olfactory stimulus. In order to determine how sensory neuronal activity is inhibited by the state of stress in both the main and accessory olfactory systems we will 1) elucidate the stress signals from the adrenal glands that are detected by olfactory sensory neurons, 2) identify the receptors on the olfactory sensory neurons that detect stress signals, and 3) determine the molecular mechanisms that enable stress to silence sensory neurons. Completion of these aims will open up new horizons to study the scope of function of olfaction. More broadly, this work will provide a molecular solution for us and others to use as a template for mechanistic study of the action of stress hormones throughout the more complicated brain. We anticipate that these results will precipitate new understanding of how sensory systems, the brain, and the body collectively generate behavior.

该提案的目标将确定内部状态的机制压力会改变神经活动。即使是最有逻辑、最聪明的人也会突然转变当充满焦虑时语无伦次。引人注目的是，百分之二十的美国成年人遭受来自使人衰弱的压力。无法忠实地找到压力反应神经元整个大脑已经阻碍了该领域发现机制的能力确切地说，压力如何影响神经元以改变行为。需要的是一个稳健的我们和其他人可以可靠地使用实验平台作为模型来研究如何压力的内部状态会改变神经功能和行为。我们的初步数据表明压力状态使神经活动的子集沉默，这些神经活动的子集易于识别、明确定义小鼠嗅觉感觉神经元的子集。神经活动的压力沉默具有对行为的黑白影响；如果一个人无法感觉到气味提示，他们就不会适当地应对环境。就其本身而言，这令人惊讶，因为认为嗅觉系统只是一个被动的感觉收集器，负责吸尘环境线索并将信息传递给大脑。相反，我们的初步数据显示，嗅觉感觉神经元能够对个体的气味做出反应当前的压力状态，并且这种反应会抑制嗅觉刺激的感觉。在为了确定压力状态如何抑制感觉神经元活动对于主要和辅助嗅觉系统，我们将 1) 阐明压力信号来自嗅觉感觉神经元检测到的肾上腺，2）识别嗅觉感觉神经元上的受体检测压力信号，3) 确定压力使感觉神经元沉默的分子机制。完成这些目标将为研究嗅觉功能范围开辟新的视野。更多的总的来说，这项工作将为我们和其他人提供一个分子解决方案作为模板用于在整个更复杂的过程中应激激素作用的机制研究脑。我们预计这些结果将促进对感官如何产生新的理解系统、大脑和身体共同产生行为。