The Role of Granule Cell Activity in Shaping Accessory Olfactory Bulb Output

颗粒细胞活性在塑造辅助嗅球输出中的作用

• 批准号: 7714711
• 负责人: Julian P Meeks
• 金额: $ 5.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7714711
• 关键词: 3-Dimensional; Accessory Olfactory Bulbs; Action Potentials; Acute; Afferent Neurons; Affinity; Area; Axon; Behavior; Brain; Cell physiology; Cells; Cellular Morphology; Characteristics; Communication; Cues; Cytoplasmic Granules; Data; Dyes; Electrodes; Electroporation; Environment; Female; Fertility; Fluorescence Microscopy; Goals; Image; Inorganic Sulfates; Label; Lateral; Learning; Length; Ligands; Link; Location; Measures; Modality; Modeling; Mus; Neurites; Neurons; Output; Pathway interactions; Pattern; Pheromone; Physiological; Play; Population; Positioning Attribute; Preparation; Process; Property; Publishing; Reporting; Research; Role; Sensory; Shapes; Signal Transduction; Smell Perception; Social Dominance; Sorting - Cell Movement; Steroids; Stimulus; Structure; Synapses; System; Testing; Thinking; Unspecified or Sulfate Ion Sulfates; Urine; Vertebrates; base; cell type; density; design; extracellular; granule cell; male; multi-photon; neural circuit; neuronal cell body; novel; olfactory bulb; response; social; steroid sulfate

Description (provided by applicant): The vomeronasal or accessory olfactory system (AOS) detects and processes pheromone signaling information from the environment. In mice, pheromonal communication is involved in establishing dominance hierarchies in males, and plays roles in promoting, synchronizing, and maintaining fertility in females. The AOS remains poorly understood compared to other communicative sensory modalities, including olfaction through the main olfactory system. Despite key differences in the neural circuitry, most of our current thinking about the AOS derives from results obtained in the main olfactory system. This research plan is designed to increase our understanding of the first central brain structure in the AOS, the accessory olfactory bulb (AOB). This application focuses on the inhibitory granule cells (GCs), which modulate the principal mitral cells of the AOB through GABAergic dendro-dendritic synapses. There are no current published reports on GC tuning to natural pheromone stimulation, despite evidence for their involvement in lateral inhibition and learning. The first Specific Aim of this application is to determine whether sensory tuning of AOB GCs is broader or sharper than tuning of vomeronasal sensory neurons (VSNs). We will determine tuning by recording action potential responses in each cell type while stimulating with sulfated steroid compounds our lab has shown to activate VSNs. We will make single extracellular electrode recordings from GCs and multi-electrode array recordings from VSNs in acute, ex vivo preparations. The second Specific Aim investigates potential links between GC morphology and physiological function. The specific connectivity patterns between mitral cells and GCs in the AOB are likely to underlie the tuning properties of each cell. We will acquire 3-dimensional morphological information from physiologically- characterized AOB GCs after labeling each recorded cell with a cytoplasmic dye. We will quantify the position, span, and density of the cell processes using fluorescence microscopy. We will use these data to determine whether structural properties correlate with specific tuning qualities of the cells. The proposed studies will fill a substantial gap in our understanding of pheromone communication in vertebrates. Relevance: Mammalian behavior is informed strongly by pheromonal communication, but little is known about how neurons in the pheromone-associated areas of the brain process social cues. This research plan investigates the responsiveness of inhibitory granule neurons in pheromone-associated brain areas in mice in order to fill a substantial gap in our understanding of this sensory pathway.

描述（由申请人提供）：vomeronasal或附件嗅觉系统（AOS）检测和处理来自环境的信息素信号信息。在小鼠中，门户交流参与建立男性的优势等级制度，并在促进，同步和维持女性的生育方面发挥作用。与其他交流感官方式相比，AOS仍然鲜为人知，包括通过主嗅觉系统的嗅觉。尽管神经回路的主要差异，但我们目前对AOS的大多数思考来自主要嗅觉系统中获得的结果。该研究计划旨在提高我们对AOS中第一个中央大脑结构的理解，即辅助嗅球（AOB）。该应用集中在抑制性颗粒细胞（GCS）上，该细胞通过GABAergic Dendro树形突触来调节AOB的主要二尖瓣细胞。尽管有证据表明它们参与了横向抑制和学习，但目前尚无有关GC调整为天然信息素刺激的报告。该应用程序的第一个具体目的是确定AOB GC的感觉调整是否比调整Vomeronasal感觉神经元（VSN）更广泛或更清晰。我们将通过记录每种细胞类型中的动作电位反应来确定调整，同时用硫酸化的类固醇化合物刺激我们的实验室表明可以激活VSN。我们将从GCS中制作单个细胞外电极记录，并从急性，离体制剂中的VSN进行多电极阵列记录。第二个特定目的研究了GC形态与生理功能之间的潜在联系。 AOB中二尖瓣和GC之间的特定连通性模式可能是每个细胞的调整特性的基础。在用细胞质染料标记每个记录的细胞后，我们将从生理特征的AOB GC中获取三维形态学信息。我们将使用荧光显微镜量化细胞过程的位置，跨度和密度。我们将使用这些数据来确定结构特性是否与细胞的特定调谐质量相关。拟议的研究将填补我们对脊椎动物信息素通信的理解。相关性：哺乳动物的行为是通过信息素养的强烈告知的，但对大脑过程的信息素相关区域中的神经元如何了解社会提示。该研究计划研究了小鼠在信息素相关的大脑区域中抑制性颗粒神经元的反应性，以填补我们对这种感觉途径的理解。