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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.

这项建议的目的将决定各种机制，压力会改变神经活动即使是最有逻辑和最聪明的人也会突然因为焦虑而语无伦次引人注目的是，20%的美国成年人从衰弱的压力。无法忠实地找到应激反应神经元已经阻碍了该领域的能力，以发现机制，压力是如何影响神经元从而改变行为的我们需要的是一个强大的我们和其他人可以可靠地使用一个实验平台作为模型来研究压力的内部状态改变神经功能和行为。我们的初步数据显示压力状态使神经活动的子集沉默，小鼠嗅觉感觉神经元的亚群。神经活动的应激沉默具有黑色和白色对行为的影响;如果一个人不能感觉到气味线索，他们就不会对环境作出适当的反应。这本身就令人惊讶，因为它一直是我认为嗅觉系统只是一个被动的感官收集器，并将信息传递给大脑。相反，我们初步的数据显示，嗅觉感觉神经元能够对个体的当前的压力状态，并且这种反应抑制嗅觉刺激的感觉。在为了确定感觉神经元活动是如何被应激状态抑制的，主要和辅助嗅觉系统，我们将1）阐明压力信号从肾上腺的嗅觉感觉神经元检测，2）确定嗅觉神经元上检测压力信号的受体，以及3）确定使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的功能范围开辟新的视野。更总的来说，这项工作将为我们和其他人提供一个分子解决方案，作为模板使用在整个更复杂的环境中，个脑袋我们预计，这些结果将促进对感官如何系统、大脑和身体共同产生行为。