CRCNS: Multiple roles of inhibition in the olfactory system

CRCNS：嗅觉系统抑制的多重作用

• 批准号: 8436620
• 负责人: MAKSIM V BAZHENOV
• 金额: $ 28.45万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436620
• 关键词: Aging; American; Anatomy; Animals; Anosmia; Area; Autistic Disorder; Award; Awareness; Back; Behavioral; Biological Models; Brain; California; Cells; Characteristics; Chemicals; Code; Complex; Computer Analysis; Computer Simulation; Computer software; Data; Detection; Development; Discrimination; Disease; Dyes; Dyslexia; Educational process of instructing; Emotions; Epilepsy; Evaluation; Event; Faculty; Feedback; Fellowship; Food; Genetic; Goals; Horns; Human; Human Resources; Immunohistochemistry; Impairment; Individual; Insecta; Institutes; Instruction; Internet; Interneurons; Invertebrates; K-12 Education; Knowledge; Laboratories; Lateral; Lead; Letters; Link; Lobe; Mathematics; Mediating; Memory; Mental disorders; Minority; Mission; Modeling; Monitor; Mushroom Bodies; Natural Gas; Neurobiology; Neurodegenerative Disorders; Neurons; Neurosciences; Odors; Output; Parkinson Disease; Pathway interactions; Physiological; Population; Postdoctoral Fellow; Process; Property; Public Health; Relative (related person); Research; Research Personnel; Research Proposals; Research Training; Role; Running; Schizophrenia; Science; Sensory; Sensory Process; Shapes; Signal Transduction; Simulate; Sleep; Smell Perception; Structure; Students; Study models; Synapses; System; Techniques; Testing; Time; Training; United States National Institutes of Health; Vertebrates; Work; awake; base; college; computational neuroscience; design; excitatory neuron; extracellular; feeding; fly; hazard; high school; hyposmia; in vivo; information processing; inhibitory neuron; insight; locust; model design; neural circuit; neuronal patterning; outreach program; programs; relating to nervous system; research study; response; tool; treatment effect; undergraduate student; web site

DESCRIPTION (provided by applicant): Collaborative research: Computational models for this project will be developed in Dr. Bazhenov's laboratory (UC Riverside). Experimental work will be conducted in Dr. Stopfer's laboratory (NIH); Dr. Stopfer is serving as a co-Investigator for this proposal. Intellectual merit: A combined experimental-computational approach will be used to reveal mechanisms of odor coding in the insect olfactory system. The main goals of the study are: 1) To resolve, using new experimental techniques and modeling approaches, a long-standing question about the significance of synchrony and oscillation in the odor processing in insect olfaction; 2) To clarify manifold and complex roles of inhibition in shaping responses of olfactory neurons. The locust and fly will be used as models for studying these different forms of inhibition in experiments involving simultaneous intracellular and multiunit recordings from Antennal Lobe (AL), Mushroom Bodies (MB) and Lateral Horn. The locust offers many advantages including the relative technical ease of making certain types of recordings. New genetic tools available only in the fly permit more detailed and specific tests of our hypotheses. Our group also has previously developed models of the locust AL and MB. Here we propose to extend these models to investigate how feedback and feed-forward inhibition may help to discriminate between similar odors, to achieve optimal odor representation across a range of concentrations, and to minimize the effects of input fluctuations. Although our existing models provide predictions and guidance, they do not yet converge with electrophysiological and behavioral data. Further, new experimental results from one of our laboratories (such as the discovery of odor-elicited oscillations in the fly AL and a reevaluation of the relative role of feedback and feed-forward inhibition in the locust MB) and other groups (such as the discovery of STDP in the locust MB) make necessary a critical re-evaluation of many previous hypotheses. We propose to achieve this with a set of carefully designed experiments to explore roles of transient oscillatory synchronization and spike coincidence detention in coding of different odors and different odor concentrations. Enhancing public health: At least 3,000,000 Americans suffer from chemosensory disorders; this number is likely to grow as the aging segment of the population increases. Olfactory impairment leads to an inability to detect hazards such as natural gas and spoiled food. Olfaction is also an important early signal of the onset of neurodegenerative diseases such as Parkinson's Disease. Broader impacts: Although the specific goal of this research proposal is to understand fundamental roles of inhibitory circuits in insect olfaction, research based on our models could be applied to study other sensory circuits, to understand and predict mechanisms responsible for oscillations and synchrony. This includes sleep rhythms and rhythmic epileptiform activity in the thalamocortical system, which have been intensively studied in Bazhenov's laboratory. One of our laboratories (Bazhenov) continuously involves undergraduate students (currently 4 students) to conduct research in the lab. This project will involve two minority undergraduate students - Martina Mikhail and Adam Jivraj - at the UCR. Martina has been working in the UCR PI lab since January 2011. She was recently awarded a summer fellowship from CAMP (California Alliance for Minority Participation) program. We expect other undergraduate students to be involved to this project as a part of their research training in the lab. Results from this new project will be included in an undergraduate lab class - Computational Neurobiology (CBNS 130L) - that is taught by the UCR PI. Furthermore, the UCR PI plans to develop a new graduate level interdisciplinary course "Computational Neuroscience of the Olfactory System" that would teach students by modeling design based on example of insect olfactory system. The relative simplicity of insect olfactory circuits allows presenting students with a complete model of olfactory processing, and to introduce fundamental ideas of synchrony and oscillations. All of the software for running the models will be made available online. UCR PI is involved in a new initiative of designing "Institute for the Application of Mathematics" at UCR that will provide cross-disciplinary training in mathematics and neuroscience. Results of this project will be used in such training. Bazhenov and postdocs employed on this award will be involved in outreach programs at UCR such as the UCR ALPHA Center (http://alphacenter.ucr.edu/mission.html) that is a facility for establishing long term engagements between faculty/campus personnel and K-12 education We will participate in the development of Web content related to this project that will become part of the ALPHA Center website. UCR participates in the Brain Awareness Week (BAW) program and we will continue this tradition by presenting results of this study during BAW events. Our other laboratory (Stopfer) regularly employs high school and college interns, and regularly provides public demonstrations of sensory science. This practice will be continued and the results of this project will be used in such events.

描述（由申请人提供）： 合作研究：该项目的计算模型将在 Bazhenov 博士的实验室（加州大学河滨分校）开发。实验工作将在Stopfer博士的实验室（NIH）进行； Stopfer 博士担任该提案的联合研究员。智力价值：将采用实验与计算相结合的方法来揭示昆虫嗅觉系统中气味编码的机制。该研究的主要目标是：1）利用新的实验技术和建模方法，解决昆虫嗅觉中气味处理中同步性和振荡的重要性这一长期存在的问题； 2）阐明抑制在塑造嗅觉神经元反应中的多种复杂作用。蝗虫和苍蝇将被用作研究这些不同形式的抑制作用的模型，这些实验涉及触角叶 (AL)、蘑菇体 (MB) 和侧角的同时细胞内和多单位记录。 Locust 具有许多优点，包括制作某些类型录音的技术相对容易。仅在果蝇中可用的新遗传工具可以对我们的假设进行更详细和具体的测试。我们组之前也开发过Locust AL和MB的模型。在这里，我们建议扩展这些模型，以研究反馈和前馈抑制如何帮助区分相似的气味，在一定浓度范围内实现最佳的气味表示，并最大限度地减少输入波动的影响。尽管我们现有的模型提供了预测和指导，但它们尚未与电生理学和行为数据融合。此外，我们的一个实验室（例如果蝇 AL 中气味引起的振荡的发现以及蝗虫 MB 中反馈和前馈抑制的相对作用的重新评估）和其他组（例如蝗虫 MB 中 STDP 的发现使得有必要对许多先前的假设进行批判性的重新评估。我们建议通过一系列精心设计的实验来实现这一目标，以探索瞬态振荡同步和尖峰重合滞留在不同气味和不同气味浓度编码中的作用。加强公共卫生：至少 3,000,000 美国人患有化学感应障碍；随着人口老龄化部分的增加，这一数字可能会增加。嗅觉障碍导致无法检测天然气和变质食物等危险。嗅觉也是帕金森病等神经退行性疾病发病的重要早期信号。更广泛的影响：虽然这项研究提案的具体目标是了解抑制回路在昆虫嗅觉中的基本作用，但基于我们的模型的研究可以应用于研究其他感觉回路，以理解和预测负责振荡和同步的机制。这包括丘脑皮质系统中的睡眠节律和节律性癫痫样活动，巴热诺夫的实验室对此进行了深入研究。我们的实验室之一（Bazhenov）不断邀请本科生（目前有 4 名学生）在实验室进行研究。该项目将涉及加州大学河滨分校的两名少数族裔本科生——Martina Mikhail 和 Adam Jivraj。 Martina 自 2011 年 1 月起一直在加州大学河滨分校 PI 实验室工作。她最近获得了 CAMP（加州少数族裔参与联盟）项目的夏季奖学金。我们希望其他本科生参与这个项目，作为他们实验室研究培训的一部分。这个新项目的结果将是 包含在本科生实验课中 - 计算神经生物学 (CBNS 130L) - 由 UCR PI 教授。此外，UCR PI 计划开发一门新的研究生水平跨学科课程“嗅觉系统的计算神经科学”，该课程将通过基于昆虫嗅觉系统示例的建模设计来教授学生。昆虫嗅觉回路相对简单，可以向学生展示嗅觉处理的完整模型，并介绍同步和振荡的基本概念。用于运行模型的所有软件都将在线提供。 UCR PI 参与了在 UCR 设计“数学应用研究所”的新举措，该研究所将提供数学和神经科学的跨学科培训。该项目的成果将用于此类培训。 Bazhenov 和获得该奖项的博士后将参与 UCR 的外展项目，例如 UCR ALPHA 中心 (http://alphacenter.ucr.edu/mission.html)，该中心是一个在教师/校园人员之间建立长期合作的设施K-12 教育 我们将参与与该项目相关的 Web 内容的开发，这些内容将成为 ALPHA 中心网站的一部分。 UCR 参加了大脑意识周 (BAW) 计划，我们将继续这一传统，在 ​​BAW 活动期间展示这项研究的结果。我们的另一个实验室（Stopfer）定期雇用高中和大学实习生，并定期提供感官科学的公开演示。这种做法将继续下去，该项目的成果将用于此类活动。