Analysis of Circuitry in the Accessory Olfactory Bulb System

附件嗅球系统电路分析

• 批准号: 7496420
• 负责人: Ken Ray Hovis
• 金额: $ 4.1万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496420
• 关键词: Accessory Olfactory Bulbs; Affect; Afferent Neurons; Antigen-Presenting Cells; Axon; Behavior; Behavioral; Behavioral Research; Binding; Brain; Calcium; Cells; Cellular Morphology; Chromosome Pairing; Complex; Dendrites; Dendritic Cells; Family; Fluorescent Dyes; Goals; Health; Heart; Heterogeneity; Hormonal; Imagery; Individual; Knowledge; Logic; Mammals; Membrane; Metabolic; Mission; Mus; Nature; Neurons; Organism; Output; Pheromone; Pheromone Receptors; Physiological; Population; Process; Stimulus; Synapses; System; Testing; Transgenic Organisms; Trees; Work; calcium indicator; receptor; research study; sensory stimulus; sensory system; vomeronasal organ

DESCRIPTION (provided by applicant): Behavioral research is at the heart of the NIH's mission of gaining fundamental knowledge about the nature and behavior of living systems. Sensory systems with simple circuitry and a direct influence on the behavior of the organism and that also apply broadly to us as complex mammals are difficult to find. The accessory olfactory system in mammals provides us with such a system with its simple circuitry and direct effect on the behavioral, hormonal and metabolic state associated with pheromones. In addition, it provides us with a simple system in which to study the organization and integration of input that directly modulates the overall behavior of higher level mammals. As is the case with any sensory system, understanding the nature of input and its representation within the system is critical to understanding how the system performs its function. In the case of the accessory olfactory system, sensory neurons in the vomeronasal organ (VNO) bind non-volatile pheromones and project and synapse on the primary output neuron (mitral cells) of the accessory olfactory bulb (AOB), in glomeruli. Determining the nature of vomeronasal sensory neuron input onto AOB mitral cells and how they represent this information is critical for understanding how this sensory system integrates and encodes information to achieve its remarkable combination of sensitivity and selectivity to affect the behavior of the organism. The overall goal of this project is to determine the rules that govern the connectivity from the VNO to the accessory olfactory bulb mitral cells. We will accomplish this goal using both electrophysiological and anatomical approaches in both transgenic V2R-GFP mice and wildtype mice. First, we will determine the degree of overlap in populations of mitral cells following stimulation of glomeruli of the same or different vomeronasal receptors types. We will test whether mitral cells receive homogenous vs. heterogenous input by comparing the degree of overlap with hypotheses for each. Second, we will analyze the dendritic tufts of mitral cells which show calcium transients upon stimulation of specific glomeruli using confocal imagery. We will determine if mitral cells send their tufts exclusively to glomeruli of the same VN receptor type or different. More importantly, understanding the logic and organization underlying these circuits allows for the identification of fundamental principles present in the great varieties of circuits found in sensory systems. These principles can then provide a conceptual framework for understanding how the brain is processing and integrating the vast amount of information it receives constantly and what goes wrong in these circuits that affects the health of individuals and their ability to receive and process sensory stimuli.

描述（由申请人提供）：行为研究是NIH使命获得有关生活系统性质和行为的基本知识的核心。具有简单电路和直接影响生物行为的感觉系统，并且很难找到复杂的哺乳动物，这也广泛适用于我们。哺乳动物中的辅助嗅觉系统为我们提供了一个简单的电路，并直接影响与信息素相关的行为，荷尔蒙和代谢状态。此外，它为我们提供了一个简单的系统，可以在其中研究输入的组织和集成，从而直接调节高级哺乳动物的整体行为。与任何感觉系统一样，了解输入的性质及其在系统中的表示对于了解系统如何执行其功能至关重要。在辅助嗅觉系统的情况下，在肾小球glomeruli中，Vomeronasal器官（VNO）中的感觉神经元结合了非挥发性信息素（VNO）在附属嗅球（AOB）的主要输出神经元（二尖瓣）上结合了突触和突触。确定对AOB二尖瓣细胞的呕吐性感觉神经元输入的性质，以及它们如何表示该信息对于理解该感觉系统如何整合和编码信息以实现其灵敏度和选择性的显着组合以影响生物体的行为至关重要。该项目的总体目标是确定控制从VNO到辅助嗅球二尖瓣细胞的连通性的规则。我们将在转基因V2R-GFP小鼠和野生型小鼠中使用电生理和解剖方法来实现这一目标。首先，我们将在刺激相同或不同的呕吐受体类型的肾小球刺激后确定二尖瓣细胞种群的重叠程度。我们将通过将重叠程度与每个假设进行比较，测试二尖瓣是否接受同质和异源输入。其次，我们将使用共共聚焦成像分析二尖瓣细胞的树突簇，这些树突簇在刺激特定肾小球时显示出钙的瞬变。我们将确定二尖瓣是否仅将其簇发送到相同的VN受体类型的肾小球或不同。更重要的是，了解这些电路的逻辑和组织可以识别感官系统中发现的大量电路中存在的基本原理。然后，这些原则可以提供一个概念框架，以了解大脑如何处理并整合其不断收到的大量信息，以及在这些电路中出了什么问题，这些电路会影响个人的健康及其接收和处理感官刺激的能力。