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

描述（由申请人提供）：表鼻或辅助嗅觉系统（AOS）检测和处理来自环境的信息素信号信息。在小鼠中，信息素交流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能力方面发挥作用。与其他交流感觉方式（包括通过主嗅觉系统的嗅觉）相比，AOS仍然知之甚少。尽管神经回路存在关键差异，但我们目前对AOS的大部分思考都来自于主嗅觉系统的研究结果。这项研究计划旨在增加我们对AOS的第一个中央大脑结构，辅助嗅球（AOB）的理解。该应用侧重于抑制颗粒细胞（GCs），其通过gaba能树突突触调节AOB的主要二尖瓣细胞。尽管有证据表明GC参与侧抑制和学习，但目前还没有关于GC调节自然信息素刺激的发表报告。该应用程序的第一个特定目的是确定AOB GCs的感觉调谐是否比犁鼻感觉神经元（VSNs）的调谐更广泛或更尖锐。我们将通过记录每种细胞类型的动作电位反应来确定调整，同时用我们实验室已经证明可以激活VSNs的硫酸类固醇化合物刺激。我们将在急性离体制剂中进行gc的单细胞外电极记录和vsn的多电极阵列记录。第二个特定目的是研究GC形态和生理功能之间的潜在联系。在AOB中二尖瓣细胞和GCs之间的特定连接模式可能是每个细胞调谐特性的基础。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中获得三维形态信息。我们将量化的位置，跨度和密度的细胞过程使用荧光显微镜。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。提出的研究将填补我们对脊椎动物信息素交流理解的实质性空白。相关性：哺乳动物的行为受到信息素交流的强烈影响，但人们对大脑中信息素相关区域的神经元如何处理社交信号知之甚少。本研究计划调查小鼠信息素相关脑区抑制颗粒神经元的反应性，以填补我们对这一感觉通路的理解的实质性空白。

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.