Assembly of the Central Olfactory Networks in Drosophila

描述（由申请人提供）：从昆虫到哺乳动物，表达相同气味受体的嗅觉受体神经元（ORN）将其轴突投射会聚到触角叶/嗅球中的特定肾小球靶点，在中枢神经系统的这些第一嗅觉结构中创建气味图。在果蝇中，触角叶投射神经元（PN，相当于脊椎动物的二尖瓣/簇状细胞）将树突发送到肾小球并与ORN轴突突触; PN轴突然后将嗅觉信息传递到更高的大脑中心蘑菇体和侧角。在过去的五年中，由于先前的资助，我们在了解果蝇嗅觉回路中的布线特异性是如何建立的方面取得了重大进展，无论是在细胞和发育事件及其分子机制方面。在这次更新中，我们提出了一系列的分子，遗传和生物化学实验，继续我们的努力，了解每个PN或ORN选择50个替代区域之一的机制，以靶向其树突或轴突，最终导致形成一个刻板的和高度精确的电路苍蝇感觉和辨别气味和信息素。我们利用候选基因方法和正向遗传筛选来鉴定这些靶向过程所需的分子，然后研究其详细的作用机制。重点将放在研究配体和受体，指导PN树突和ORN轴突在触角叶的适当地区，并faciliate他们的突触匹配。我们期望，在此资助的拟议实验的完成将显着丰富和扩大我们的嗅觉电路组装的逻辑和机制的理解。这些研究将有助于我们理解一些重要的神经生物学问题，包括神经元的命运规范，树突状细胞的指导和目标，以及嗅觉回路和神经回路的组装逻辑。我们的研究也将提供深入了解嗅觉信息是如何沿着中央通路传递和转化的。了解神经回路在正常发育过程中是如何连接的，是了解病理性连接本质的先决条件，病理性连接是许多人类神经和精神疾病的基础。此外，昆虫嗅觉系统的组织和发展的知识可以用来帮助设计战略，以打击疟疾，传播的蚊子，主要利用嗅觉来寻找他们的配偶和人类宿主。

DESCRIPTION (provided by applicant): From insects to mammals, olfactory receptor neurons (ORNs) expressing the same odorant receptors converge their axonal projections to specific glomerular targets in the antennal lobe/olfactory bulb, creating an odor map in these first olfactory structures of the central nervous system. In the fruit fly Drosophila, antennal lobe projection neurons (PNs, equivalent to vertebrate mitral/tufted cells) send dendrites to glomeruli and synapse with ORN axons; PN axons then relay the olfactory information to higher brain centers the mushroom body and the lateral horn. Over the past five years and thanks to the support of the previous grant, we have made significant progress towards understanding how wiring specificity in the Drosophila olfactory circuit is established, both in terms of cellular and developmental events and their molecular mechanisms. In this renewal, we propose a series of molecular, genetic and biochemical experiments to continue our effort in understanding the mechanisms by which each PN or ORN chooses one of 50 alternative areas to target its dendrites or axons, ultimately resulting in the formation of a stereotyped and highly precise circuit for flies to sense and discriminate odors and pheromones. We utilize both candidate gene approaches and forward genetic screen to identify molecules that are required for these targeting processes, and then investigate their detailed mechanisms of action. Emphasis will be placed on studying ligands and receptors that guide PN dendrites and ORN axons to appropriate areas in the antennal lobe and faciliate their synaptic matching. We expect that completion of the proposed experiments in this grant will significantly enrich and expand our understanding of the logic and mechanisms of olfactory circuit assembly. These studies will contribute to our understanding of a number of important neurobiological questions, including neuronal fate specification, dendritic guidance and targeting, and the logic of the assembly of the olfactory circuits and neural circuits in general. Our studies will also provide insight into how olfactory information is transferred and transformed along the central pathways. PUBLIC HEALTH RELEVANCE Understanding how neural circuits are wired during normal development is a prerequisite for understanding the nature of pathological wiring, which underlie many human neurological and psychiatric disorders. In addition, knowledge of insect olfactory system organization and development can be used to help design strategies to combat malaria, transmitted by mosquitos that utilize primarily olfaction to find their mates and human host.