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（UC滨江）开发。实验工作将在Stopfer博士的实验室（NIH）进行; Stopfer博士是该提案的共同研究者。智力优势：将采用实验与计算相结合的方法来揭示昆虫嗅觉系统中的气味编码机制。本研究的主要目的是：1）利用新的实验技术和建模方法，解决昆虫嗅觉中气味加工的同步性和振荡性的重要性这一长期存在的问题; 2）阐明抑制在嗅觉神经元形成反应中的多种复杂作用。蝗虫和苍蝇将被用来作为模型，研究这些不同形式的抑制在实验中，涉及同时细胞内和多单元记录从肺叶（AL），蘑菇体（MB）和侧角。蝗虫提供了许多优势，包括相对容易的技术，使某些类型的录音。新的遗传工具只在苍蝇允许更详细和具体的测试我们的假设。我们的小组以前也开发了蝗虫AL和MB的模型。在这里，我们建议扩展这些模型来研究如何反馈和前馈抑制可能有助于区分类似的气味，以实现最佳的气味表示在一个范围内的浓度，并尽量减少输入波动的影响。虽然我们现有的模型提供了预测和指导，但它们还没有与电生理和行为数据相融合。此外，新的实验结果，从我们的实验室之一（如发现的气味引起的振荡在苍蝇AL和反馈和前馈抑制蝗虫MB的相对作用的重新评估）和其他团体（如发现STDP蝗虫MB）有必要重新评估许多以前的假设。我们建议实现这一点，一组精心设计的实验，探讨瞬态振荡同步和尖峰重合滞留在不同的气味和不同的气味浓度的编码的作用。加强公共卫生：至少有3，000，000名美国人患有化学感觉障碍;随着人口老龄化的增加，这个数字可能会增加。嗅觉障碍导致无法检测天然气和变质食物等危险。嗅觉也是神经退行性疾病如帕金森病发作的重要早期信号。更广泛的影响：虽然这项研究计划的具体目标是了解抑制回路在昆虫嗅觉中的基本作用，但基于我们模型的研究可以应用于研究其他感觉回路，了解和预测负责振荡和同步的机制。这包括睡眠节律和丘脑皮质系统中的节律性癫痫样活动，这些都在巴热诺夫的实验室进行了深入研究。我们的一个实验室（巴热诺夫）不断涉及本科生（目前4名学生）在实验室进行研究。该项目将涉及两名少数民族本科生-玛蒂娜米哈伊尔和亚当Jivraj -在加州大学河滨分校。Martina自2011年1月以来一直在UCR PI实验室工作。她最近获得了CAMP（加州少数民族参与联盟）项目的暑期奖学金。我们希望其他本科生参与这个项目，作为他们在实验室的研究培训的一部分。这一新项目的成果将是 包括在一个本科实验室类-计算神经生物学（CBNS 130 L）-这是由UCR PI教授。此外，UCR PI计划开发一个新的研究生水平的跨学科课程“嗅觉系统的计算神经科学”，将教授学生基于昆虫嗅觉系统的例子建模设计。昆虫嗅觉回路的相对简单性允许向学生呈现嗅觉处理的完整模型，并介绍同步和振荡的基本思想。所有运行模型的软件都将在网上提供。UCR PI参与了一项新的倡议，即在UCR设计“数学应用研究所”，该研究所将提供数学和神经科学方面的跨学科培训。该项目的成果将用于此类培训。Bazhenov和博士后受聘于此奖项将参与外展计划在UCR如UCR阿尔法中心（http：//bazhenacenter.ucr.edu/mission.html），这是一个设施，建立教师/校园人员和K-12教育之间的长期约定，我们将参与与该项目相关的网络内容的发展，将成为阿尔法中心网站的一部分。UCR参加了大脑意识周（BAW）计划，我们将通过在BAW活动期间展示这项研究的结果来延续这一传统。我们的另一个实验室（Stopfer）定期雇用高中和大学实习生，并定期提供感官科学的公开演示。这一做法将继续下去，这一项目的成果将用于这类活动。