RUI: Compensatory Plasticity in the Olfactory System

RUI：嗅觉系统的补偿可塑性

• 批准号: 0641433
• 负责人: David Coppola
• 金额: $ 37.5万
• 依托单位: Randolph-Macon College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0641433&HistoricalAwards=false
• 关键词: RUI; Compensatory; Plasticity; Olfactory; System

Neural activity, either sensory driven or endogenous, is critical for the development and functional maintenance of many parts of the nervous system. For example, if sensory input is eliminated during a critical period in early life, primary sensory areas in the brain can be malformed, sometimes irreversibly. Given the importance of continued sensory input to the nervous system, it seems likely that sensory receptor cells would evolve compensatory responses to sensory deprivation. In fact, recent evidence suggests that neurons in many areas of the nervous system display 'homeostaticplasticity' such that their intrinsic excitability is altered by experience. In the developing olfactory system, occluding one side of the nasal cavity, and thus reducing odor stimulation to olfactory receptor neurons, alters the development of olfactory pathways receiving input from these receptors. Recently, it was discovered that adenylyl cyclase three (ACIII), Olfactory Marker Protein (OMP), and a phopshodiesterase (PDE4A), all proteins known to play a role in olfactory transduction, increase in concentration in olfactory receptor neurons following sensory deprivation. These results imply that olfactory receptors, like many other neurons, have a compensatory response to stimulus deprivation. To further evaluate this hypothesis, the PI and collaborators will: (1) use immunocytochemistry and Western blotting for OMP, PDE4A, ACIII, and other transductory elements to confirm and extend preliminary findings, (2) compare electro-olfactograms (EOGs) recorded from olfactory receptor neurons on the occluded and non-occluded sides of the nasal cavity, and (3) measure the psychophysical capabilities of mice that have undergone olfactory deprivation by naris occlusion. Taken together, the results of these studies will help establish a previously unknown compensatory plasticity in the olfactory system, shed light on the role of OMP, PDE4A, and other proteins involved in odor transduction, and clarify the roll of experience in the developing and adult olfactory system. In addition to their inherent intellectual merits, the proposed activities are designed to have a broader impact in that they will enhance the culture of science at Randolph-Macon College, a small liberal arts institution, by increasing the opportunities for students to participate in independent research. Also, this award will improve the College's research infrastructure by providing equipment that will be foundational for an emerging undergraduate research initiative. This grant is part of a major thrust by the College's Science Division to revise the science curriculum such that student learning is more hands-on, open-ended, and interdisciplinary. Proposed activities to improve the culture of science are focused on graduate and medical school bound students but will also be of interest to other science and non-science majors. Students completing independent research projects will use the requested equipment and will benefit from the requested summer stipends, funds for supplies, and funds for meeting attendance. In addition to the broader impact at Randolph-Macon, this award will allow the PI and participating college students to improve the college preparation of a group of inner-city high school students and, hopefully, increase the number of qualified college-bound minority students in the pipeline. Lastly, this award will foster collaborations between Randolph-Macon College, targeted inner-city schools, and a regional research center, Virginia Commonwealth University.

神经活动，无论是感觉驱动的还是内源性的，对于神经系统的许多部分的发育和功能维持都是至关重要的。例如，如果感觉输入在生命早期的关键时期被消除，大脑中的初级感觉区域可能会畸形，有时是不可逆的。鉴于持续的感觉输入对神经系统的重要性，感觉受体细胞似乎会对感觉剥夺产生补偿反应。事实上，最近的证据表明，神经系统许多区域的神经元都表现出“稳态可塑性”，它们的内在兴奋性会因经验而改变。在发育中的嗅觉系统中，封闭鼻腔的一侧，从而减少对嗅觉受体神经元的气味刺激，改变了从这些受体接收输入的嗅觉通路的发育。 最近，发现腺苷酸环化酶3（ACIII）、嗅觉标记蛋白（OMP）和磷酸二酯酶（PDE 4A）（所有已知在嗅觉传导中起作用的蛋白质）在感觉剥夺后在嗅觉受体神经元中的浓度增加。这些结果表明，嗅觉受体，像许多其他神经元，有一个补偿性反应，刺激剥夺。为了进一步评估该假设，PI和合作者将：（1）对OMP、PDE 4A、ACIII和其他转导元件使用免疫细胞化学和蛋白质印迹法以确认和扩展初步发现，（2）比较从鼻腔的阻塞侧和非阻塞侧上的嗅觉受体神经元记录的嗅觉电图（EOG），和（3）测量通过鼻孔阻塞进行嗅觉剥夺的小鼠的心理物理能力。 综上所述，这些研究的结果将有助于建立一个以前未知的补偿性可塑性嗅觉系统，阐明OMP，PDE 4A，和其他蛋白质参与气味转导的作用，并澄清辊的经验在发展和成人嗅觉系统。 除了其固有的知识价值外，拟议的活动旨在产生更广泛的影响，因为它们将通过增加学生参与独立研究的机会，加强Randolph-Macon学院这一小型文科院校的科学文化。此外，该奖项将改善学院的研究基础设施，提供设备，这将是一个新兴的本科生研究计划的基础。这笔赠款是由学院的科学司修改科学课程，使学生学习更多的动手，开放式和跨学科的主要推力的一部分。拟议的提高科学文化的活动主要针对研究生和医学院的学生，但其他科学和非科学专业的学生也会感兴趣。完成独立研究项目的学生将使用所要求的设备，并将受益于所要求的夏季津贴，用品资金和会议出席资金。除了在伦道夫-梅肯更广泛的影响，这个奖项将允许PI和参与的大学生，以提高一组内城高中学生的大学准备，并希望，增加合格的大学数量在管道中的少数民族学生。最后，该奖项将促进伦道夫-梅肯学院，有针对性的内城学校和区域研究中心，弗吉尼亚联邦大学之间的合作。