CRCNS: Multiple roles of inhibition in the olfactory system

CRCNS：嗅觉系统抑制的多重作用

基本信息

批准号：
9091558
负责人：
MAKSIM V BAZHENOV
金额：
$ 26.49万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9091558
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 Electrophysiology (science)Emotions Epilepsy Evaluation Event Faculty Feedback Fellowship Food Genetic Goals Hodgkin-Huxley model Horns Human Human Resources Immunohistochemistry Impairment Individual Insecta Institutes Instruction Internet Interneurons Internships Invertebrates K-12 Education Knowledge Laboratories Lateral Lead Letters Link Lobe Mathematics Mediating Memory Mental disorders Minority Participation Mission Modeling Monitor Mushroom Bodies Natural Gas Neurobiology Neurodegenerative Disorders Neurons Neurosciences Odors Olfactory Pathways Output Parkinson Disease Pathway interactions Physiological Population Postdoctoral Fellow Process Property Public Health Research Research Personnel Research Proposals Research Training Role Running Schizophrenia Science Sensory Sensory Process Shapes Signal Transduction 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 mathematical analysis minority undergraduate model design neural circuit neuronal circuitry neuronal patterning outreach program programs relating to nervous system research study response tool treatment effect undergraduate student web site

项目摘要

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）：协作研究：该项目的计算模型将在Bazhenov博士的实验室（UC Riverside）中开发。实验性工作将在Stopfer博士的实验室（NIH）中进行； Stopfer博士正在作为该提案的共同投资者。智力优点：将使用合并的实验计算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）使用新的实验技术和建模方法解决，这是一个关于同步和振荡在气味加工昆虫嗅觉中的重要性的长期问题； 2）阐明抑制在嗅觉神经元的塑造反应中的歧管和复杂作用。蝗虫和苍蝇将用作研究这些不同形式的抑制作用的模型，这些抑制作用涉及触角叶（AL），蘑菇体（MB）和侧角的同时细胞内和多单位记录。蝗虫提供了许多优势，包括相对的技术简便性制作某些类型的录音。仅在飞行中可用的新遗传工具允许对我们的假设进行更多详细和具体的测试。我们的小组也以前已经开发了蝗虫AL和MB的模型。在这里，我们建议扩展这些模型，以调查反馈和前馈抑制如何有助于区分相似的气味，从而在一系列浓度范围内实现最佳的气味表示，并最大程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和行为数据相聚。此外，我们的一个实验室（例如在苍蝇中发现了被气味引起的振荡的新实验结果，并重新评估了反馈和远前抑制在蝗虫MB中的相对作用）和其他群体（例如，在locust MB中发现STDP在MB中发现）使得必要的重新评估以前的许多低迷。我们建议通过一组精心设计的实验来实现这一目标，以探索瞬时振荡同步和尖峰巧合限制在不同气味和不同气味浓度的编码中的作用。增强公共卫生：至少有3,000,000名美国人患有化学感应障碍；随着人口的老化段的增加，这个数字可能会增加。嗅觉损害导致无法检测诸如天然气和宠坏食物之类的危害。嗅觉也是神经退行性疾病（如帕金森氏病）发作的重要早期信号。更广泛的影响：尽管该研究建议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电路，以了解和预测负责振荡和同步的机制。这包括在丘脑皮质系统中的睡眠节律和节奏性癫痫样活性，这些活性已在Bazhenov的实验室进行了深入研究。我们的一位实验室（Bazhenov）不断涉及本科生（目前4名学生）在实验室进行研究。该项目将在UCR上涉及两名少数族裔本科生-Martina Mikhail和Adam Jivraj。 Martina自2011年1月以来一直在UCR PI实验室工作。最近，她获得了CAMP（加利福尼亚州少数民族参与）计划的夏季奖学金。我们希望其他本科生将参与该项目，作为他们在实验室中研究培训的一部分。这个新项目的结果将是包括在UCR PI教授的本科实验室类 - 计算神经生物学（CBNS 130L）中。此外，UCR PI计划开发新的研究生级跨学科课程“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的示例来建模设计来教学学生。昆虫嗅觉电路的相对简单性允许向学生提供完整的嗅觉处理模型，并引入同步和振荡的基本思想。所有用于运行模型的软件将在线提供。 UCR PI参与了UCR设计“数学应用研究所”的一项新计划，该计划将提供数学和神经科学方面的跨学科培训。该项目的结果将用于此类培训。该奖项雇用的Bazhenov和博士后将参与UCR的外展计划，例如UCR Alpha Center（http://alphacenter.ucr.ucr.edu/mission.html），这些设施是建立长期参与的设施，以建立长期参与的教师/校园人员和K-12教育之间的网站与Web内容相关的网站，该项目与该项目有关。 UCR参加了大脑意识周（BAW）计划，我们将通过在BAW活动期间提出这项研究的结果来继续这一传统。我们的另一个实验室（Stopfer）定期雇用高中和大学实习生，并定期提供有关感官科学的公开演示。这种做法将继续，该项目的结果将在此类事件中使用。