RUI, ABR: Olfactory Compensatory Plasticity

神经系统根据经验而改变的能力，即表现出“可塑性”，是神经科学研究的一个长期课题。特别是，持续的感觉刺激对感觉系统的正常发育和维持的作用是一个长期感兴趣的领域。关于嗅觉的这些过程的知识落后于其他感官，尤其是因为在物理上控制气味刺激是困难的。这个项目促进了我们对刺激引起的变化的理解，嗅觉处理和其他嗅觉机制，以及揭示了生理系统的趋势，如嗅觉，在相互依赖的元素之间相对稳定的平衡中运作，这个过程被称为体内平衡。嗅觉外围提供了一个很好的模型，在这个模型中，可以确定稳态系统的所有组成部分。除了推进我们对嗅觉和感觉可塑性的理解之外，这些研究还可能为化学检测设备（“电子鼻”）提供设计元素，应用于机器人、疾病诊断和炸弹探测。与研究项目相结合的是学生指导、扩大参与、通过本科生（包括代表性不足群体的成员）的积极参与进行公众宣传，以及在当地儿童博物馆举办展览。该项目的这些方面改善了科学、技术、工程和数学方面的人力资源，并且通过博物馆，每年可能吸引数千名学生。这个项目解决了我们的感官如何适应刺激环境的长期变化的普遍问题。这种适应性使感觉系统能够将其感受器的动态范围与环境中的一系列刺激相匹配，这些刺激可能在时间和空间上发生巨大变化。对这些类内稳态过程的细胞机制知之甚少。研究者和他的同事们在嗅觉外围发现了一种被称为代偿可塑性的现象，这种现象具有这种过程的特征。在嗅觉上皮中，气味剥夺导致转导级联的上调和生理反应的增强，似乎在低刺激环境中进行补偿。以前的工作只允许对气味环境进行二元控制（即剥夺或不剥夺）。在当前的项目中，嗅觉系统对气味刺激历史的反应是使用嗅觉测量方法来检查的，这种方法允许更广泛地控制气味环境，包括气味暴露的类型、复杂性、浓度和时间。依赖的测量包括转录组，组织学，生理和行为终点，允许对代偿可塑性的整体分析，为这一过程的机制理解奠定基础。这些研究结果促进了我们对嗅觉可塑性的认识，并阐明了神经可塑性和内稳态的机制

The ability of the nervous system to change in response to experience, i.e., to exhibit 'plasticity', is a long-standing topic of inquiry in neuroscience. In particular, the role of ongoing sensory stimulation for the normal development and maintenance of sensory systems is a perennial area of interest. Knowledge about these processes for the sense of smell lags behind the other senses, not least because of the difficulty in physically controlling an odor stimulus. This project advances our understanding of stimulus-induced changes olfactory processing and other mechanisms of smell, as well as sheds light on the tendency of physiological systems, like olfaction, to operate in a relatively stable equilibrium between interdependent elements, the process known as homeostasis. The olfactory periphery affords an excellent model where all components of a homeostatic system can be ascertained. Besides advancing our understanding of the sense of smell and sensory plasticity, the studies may suggest design elements for incorporation into chemical detection devices ('electronic noses') with applications in robotics, disease diagnosis, and bomb detection. Integrated with the research project is student-mentoring, participation-broadening, and public outreach through active involvement of undergraduates, including members of underrepresented groups, and the development of an exhibit at a local children's museum. These aspects of the project improve human resources in Science, Technology, Engineering, and Mathematics, and, via the museum, may engage thousands of school students annually. This project addresses the universal problem of how our senses adjust to long-term changes in the stimulus environment. Such adaptability allows sensory systems to match the dynamic range of their receptors to the array of stimuli in the environment, which can vary dramatically in time and space. Little is known about the cellular mechanisms of these homeostasis-like processes. The Investigator and his colleagues have discovered a phenomenon in the olfactory periphery termed compensatory plasticity that has the signature of such a process. In the olfactory epithelium, odor deprivation causes an up-regulation of the transduction cascade and enhancement of physiological responses that seemingly compensate in low stimulus environments. The previous work allowed only binary control of the odor environment (i.e., deprivation or no deprivation). In the current project, the responses of the olfactory system to odor stimulation history is examined using olfactometric methods that allow broader control of odor environments, including the type, complexity, concentration, and timing of odor exposure. The dependent measures include transcriptomic, histological, physiological, and behavior endpoints, allowing a holistic analysis of compensatory plasticity that lays the groundwork for a mechanistic understanding of this process. Results from these studies advance our understanding of olfactory plasticity as well as illuminate mechanisms of neural plasticity and homeostasis