RUI: Compensatory Plasticity in the Olfactory System

神经活动，无论是感觉驱动的还是内源性的，对神经系统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，大脑中的主要感觉区域可能会畸形，有时是不可逆转的。鉴于持续的感觉输入对神经系统的重要性，感觉感受器细胞似乎可能会进化出对感觉剥夺的补偿反应。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”，以至于它们内在的兴奋性会因经验而改变。在发育中的嗅觉系统中，阻塞一侧鼻腔，从而减少对嗅觉感受器神经元的气味刺激，改变了接受这些受体输入的嗅觉通路的发育。最近发现，在嗅觉剥夺后，在嗅觉传导中起作用的腺酰环化酶3(ACIII)、嗅标记物蛋白(OMP)和磷酸二酯酶(PDE4A)在嗅觉感受器神经元中的浓度升高。这些结果表明，嗅觉感受器和许多其他神经元一样，对刺激剥夺有代偿反应。为了进一步评估这一假说，PI及其合作者将：(1)使用免疫细胞化学和Western blotting对OMP、PDE4A、ACIII和其他传导元件进行确认和扩展，(2)比较鼻腔阻塞和非阻塞侧嗅觉感受器神经元记录的电嗅图(EOGs)；以及(3)测量因鼻孔阻塞而遭受嗅觉剥夺的小鼠的心理物理能力。综上所述，这些研究结果将有助于在嗅觉系统中建立一种以前未知的代偿性可塑性，阐明OMP、PDE4A和其他参与气味转导的蛋白质的作用，并澄清在发育和成人嗅觉系统中的经验。除了其固有的智力优势外，拟议的活动还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，加强小型文科机构伦道夫-梅肯学院的科学文化。此外，该奖项将通过提供为新兴的本科生研究计划奠定基础的设备来改善学院的研究基础设施。这笔拨款是学院科学部修订科学课程的主要努力的一部分，以使学生的学习更具实践性、开放性和跨学科性质。拟议的提高科学文化的活动侧重于研究生和医学院学生，但也将对其他理科和非理科专业的学生感兴趣。完成独立研究项目的学生将使用所要求的设备，并将从所要求的暑期津贴、用品资金和参加会议的资金中受益。除了对伦道夫-梅肯学院更广泛的影响外，这一奖项还将允许PI和参与其中的大学生改善一批市中心高中生的大学准备工作，并有望增加有资格进入大学的少数民族学生的数量。最后，这一奖项将促进伦道夫-梅肯学院、针对市中心学校的合作，以及地区研究中心弗吉尼亚联邦大学之间的合作。

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.