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: 7615215
• 负责人: Julian P Meeks
• 金额: $ 5.01万
• 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/7615215
• 关键词: 3-Dimensional; Accessory Olfactory Bulbs; Action Potentials; Acute; Afferent Neurons; Affinity; Antigen-Presenting Cells; Area; Axon; Behavior; Brain; Cell Density; Cell physiology; Cells; Cellular Morphology; Characteristics; Chromosome Pairing; Class; 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; Numbers; Output; Pathway interactions; Pattern; Pheromone; Physiological; Placement; Population; Positioning Attribute; Preparation; Process; Property; Publishing; Range; Reporting; Research; Role; Role playing therapy; 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; 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）：犁鼻器或辅助嗅觉系统（AOS）检测和处理来自环境的信息素信号信息。在小鼠中，信息素通信参与建立雄性的统治等级，并在促进、同步和维持雌性的生育力方面发挥作用。与其他交流感觉方式（包括通过主要嗅觉系统的嗅觉）相比，AOS仍然知之甚少。尽管在神经回路中存在关键差异，但我们目前对AOS的大多数想法都来自主要嗅觉系统中获得的结果。这项研究计划旨在增加我们对AOS中的第一个中枢脑结构，即副嗅球（AOB）的了解。本申请集中于抑制性颗粒细胞（GC），其通过GABA能树突-树突突触调节AOB的主要二尖瓣细胞。有没有目前发表的报告GC调谐到天然信息素刺激，尽管有证据表明他们参与侧抑制和学习。本申请的第一个具体目的是确定AOB GC的感觉调谐是否比犁鼻感觉神经元（VSN）的调谐更宽或更尖锐。我们将通过记录每种细胞类型的动作电位反应来确定调谐，同时用我们实验室已经证明可以激活VSN的硫酸化类固醇化合物进行刺激。我们将在急性离体制备中从GC和VSN的多电极阵列记录中进行单个细胞外电极记录。第二个特定目的研究GC形态和生理功能之间的潜在联系。AOB中二尖瓣细胞和GC之间的特定连接模式可能是每个细胞的调谐特性的基础。我们将在用细胞质染料标记每个记录的细胞后，从生理学表征的AOB GC获得三维形态信息。我们将使用荧光显微镜量化细胞突起的位置、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品质相关。拟议的研究将填补一个实质性的空白，我们的理解信息素通信的脊椎动物。相关性：哺乳动物的行为强烈地受到信息素交流的影响，但人们对大脑中与信息素相关的区域的神经元如何处理社会线索知之甚少。这项研究计划调查了小鼠信息素相关脑区抑制性颗粒神经元的反应性，以填补我们对这种感觉通路的理解中的一个重大空白。